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class="interlanguage-link-target"><span>العربية</span></a></li><li class="interlanguage-link interwiki-cs mw-list-item"><a href="https://cs.wikipedia.org/wiki/PD-1" title="PD-1 – Czech" lang="cs" hreflang="cs" data-title="PD-1" data-language-autonym="Čeština" data-language-local-name="Czech" class="interlanguage-link-target"><span>Čeština</span></a></li><li class="interlanguage-link interwiki-cy mw-list-item"><a href="https://cy.wikipedia.org/wiki/PDCD1" title="PDCD1 – Welsh" lang="cy" hreflang="cy" data-title="PDCD1" data-language-autonym="Cymraeg" data-language-local-name="Welsh" class="interlanguage-link-target"><span>Cymraeg</span></a></li><li class="interlanguage-link interwiki-de mw-list-item"><a href="https://de.wikipedia.org/wiki/Programmed_Cell_Death_Protein_1" title="Programmed Cell Death Protein 1 – German" lang="de" hreflang="de" data-title="Programmed Cell Death Protein 1" data-language-autonym="Deutsch" data-language-local-name="German" class="interlanguage-link-target"><span>Deutsch</span></a></li><li class="interlanguage-link interwiki-et mw-list-item"><a href="https://et.wikipedia.org/wiki/PD-1" title="PD-1 – Estonian" lang="et" hreflang="et" data-title="PD-1" data-language-autonym="Eesti" data-language-local-name="Estonian" class="interlanguage-link-target"><span>Eesti</span></a></li><li class="interlanguage-link interwiki-fa mw-list-item"><a href="https://fa.wikipedia.org/wiki/PD-1" title="PD-1 – Persian" lang="fa" hreflang="fa" data-title="PD-1" data-language-autonym="فارسی" data-language-local-name="Persian" class="interlanguage-link-target"><span>فارسی</span></a></li><li class="interlanguage-link interwiki-fr mw-list-item"><a href="https://fr.wikipedia.org/wiki/Prot%C3%A9ine_1_de_la_mort_cellulaire_programm%C3%A9e" title="Protéine 1 de la mort cellulaire programmée – French" lang="fr" hreflang="fr" data-title="Protéine 1 de la mort cellulaire programmée" data-language-autonym="Français" data-language-local-name="French" class="interlanguage-link-target"><span>Français</span></a></li><li class="interlanguage-link interwiki-ko mw-list-item"><a href="https://ko.wikipedia.org/wiki/PD-1" title="PD-1 – Korean" lang="ko" hreflang="ko" data-title="PD-1" data-language-autonym="한국어" data-language-local-name="Korean" class="interlanguage-link-target"><span>한국어</span></a></li><li class="interlanguage-link interwiki-it mw-list-item"><a href="https://it.wikipedia.org/wiki/Proteina_1_della_morte_cellulare_programmata" title="Proteina 1 della morte cellulare programmata – Italian" lang="it" hreflang="it" data-title="Proteina 1 della morte cellulare programmata" data-language-autonym="Italiano" data-language-local-name="Italian" class="interlanguage-link-target"><span>Italiano</span></a></li><li class="interlanguage-link interwiki-ja mw-list-item"><a href="https://ja.wikipedia.org/wiki/PD-1" title="PD-1 – Japanese" lang="ja" hreflang="ja" data-title="PD-1" data-language-autonym="日本語" 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noprint searchaux" style="display:none">Mammalian protein found in humans</div> <p class="mw-empty-elt"> </p> <table class="infobox" style="width:26.4em"><tbody><tr><th colspan="4" style="text-align:center;font-size:125%;font-weight:bold">PDCD1</th></tr><tr><td colspan="4" style="text-align:center"><span typeof="mw:File"><a href="/wiki/File:PD-1_ribbon_3RRQ.png" class="mw-file-description"><img src="//upload.wikimedia.org/wikipedia/commons/thumb/a/aa/PD-1_ribbon_3RRQ.png/250px-PD-1_ribbon_3RRQ.png" decoding="async" width="250" height="195" class="mw-file-element" srcset="//upload.wikimedia.org/wikipedia/commons/thumb/a/aa/PD-1_ribbon_3RRQ.png/500px-PD-1_ribbon_3RRQ.png 1.5x" data-file-width="2247" data-file-height="1755" /></a></span></td></tr><tr><td colspan="4" style="text-align:center;background-color:light-dark(#eee, #27292d) !important;color:inherit"><table style="padding:0;border:none;margin:0;width:100%;text-align:left"><tbody><tr><th colspan="4" style="text-align:center;background-color:light-dark(#ddd, #404244) !important;color:inherit">Available structures</th></tr><tr><th rowspan="2" style="background-color:light-dark(#c3fdb8, #003500) !important;color:inherit;width:43px"><a href="/wiki/Protein_Data_Bank" title="Protein Data Bank">PDB</a></th><td colspan="2" style="background-color:light-dark(#eee, #27292d) !important;color:inherit">Ortholog search: <span class="plainlinks"><a rel="nofollow" class="external text" href="https://www.ebi.ac.uk/pdbe/searchResults.html?display=both&term=Q02242%20or%20Q15116">PDBe</a> <a rel="nofollow" class="external text" href="https://www.rcsb.org/search?q=rcsb_polymer_entity_container_identifiers.reference_sequence_identifiers.database_name:UniProt%20AND%20rcsb_polymer_entity_container_identifiers.reference_sequence_identifiers.database_accession:Q02242,Q15116">RCSB</a> </span></td></tr><tr><td><table class="collapsible collapsed" style="padding:0;border:none;margin:0;width:100%;text-align:left"><tbody><tr style="text-align:center"><th colspan="2" style="background-color:light-dark(#ddd, #404244) !important;color:inherit">List of PDB id codes</th></tr><tr><td colspan="2" style="background-color:light-dark(#eee, #27292d) !important;color:inherit"><p><span class="plainlinks"><a rel="nofollow" class="external text" href="https://www.rcsb.org/structure/2M2D">2M2D</a>, <a rel="nofollow" class="external text" href="https://www.rcsb.org/structure/3RRQ">3RRQ</a>, <a rel="nofollow" class="external text" href="https://www.rcsb.org/structure/4ZQK">4ZQK</a></span></p></td></tr></tbody></table></td></tr></tbody></table></td></tr><tr><th colspan="4" style="text-align:center;background-color:light-dark(#ddd, #404244) !important;color:inherit">Identifiers</th></tr><tr><th scope="row" style="background-color:light-dark(#c3fdb8, #003500) !important;color:inherit"><span class="plainlinks"><a href="/wiki/Gene_nomenclature" title="Gene nomenclature">Aliases</a></span></th><td colspan="3" style="background:light-dark(#eee, #27292d) !important;color:inherit"><span class="plainlinks"><a rel="nofollow" class="external text" href="https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/8760">PDCD1</a></span>, CD279, PD-1, PD1, SLEB2, hPD-1, hPD-l, hSLE1, Programmed cell death 1</td></tr><tr><th scope="row" style="background-color:light-dark(#c3fdb8, #003500) !important;color:inherit">External IDs</th><td colspan="3" style="background-color:light-dark(#eee, #27292d) !important;color:inherit"><span class="plainlinks"><a href="/wiki/Mendelian_Inheritance_in_Man" class="mw-redirect" title="Mendelian Inheritance in Man">OMIM</a>: <a rel="nofollow" class="external text" href="https://omim.org/entry/600244">600244</a>; <a href="/wiki/Mouse_Genome_Informatics" title="Mouse Genome Informatics">MGI</a>: <a rel="nofollow" class="external text" href="http://www.informatics.jax.org/marker/MGI:104879">104879</a>; <a href="/wiki/HomoloGene" title="HomoloGene">HomoloGene</a>: <a rel="nofollow" class="external text" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=homologene&dopt=HomoloGene&list_uids=3681">3681</a>; <a href="/wiki/GeneCards" title="GeneCards">GeneCards</a>: <a rel="nofollow" class="external text" href="https://www.genecards.org/cgi-bin/carddisp.pl?gene=PDCD1">PDCD1</a>; <a href="/wiki/Orthologous_MAtrix" title="Orthologous MAtrix">OMA</a>:<a rel="nofollow" class="external text" href="https://omabrowser.org/oma/vps/ENSG00000188389">PDCD1 - orthologs</a></span></td></tr><tr><td colspan="4" style="text-align:center;background-color:light-dark(#eee, #27292d) !important;color:inherit"><table class="collapsible collapsed" style="padding:0;border:none;margin:0;width:100%;text-align:left"><tbody><tr><th colspan="4" style="text-align:center;background-color:light-dark(#ddd, #404244) !important;color:inherit">Gene location (<a href="/wiki/Human_genome" title="Human genome">Human</a>)</th></tr><tr><td colspan="4" style="text-align:center;background-color:light-dark(#eee, #27292d) !important;color:inherit"><span typeof="mw:File"><a href="/wiki/File:Ideogram_human_chromosome_2.svg" class="mw-file-description" title="Chromosome 2 (human)"><img alt="Chromosome 2 (human)" src="//upload.wikimedia.org/wikipedia/commons/thumb/a/aa/Ideogram_human_chromosome_2.svg/330px-Ideogram_human_chromosome_2.svg.png" decoding="async" width="300" height="120" class="mw-file-element" srcset="//upload.wikimedia.org/wikipedia/commons/thumb/a/aa/Ideogram_human_chromosome_2.svg/450px-Ideogram_human_chromosome_2.svg.png 1.5x, //upload.wikimedia.org/wikipedia/commons/thumb/a/aa/Ideogram_human_chromosome_2.svg/600px-Ideogram_human_chromosome_2.svg.png 2x" data-file-width="474" data-file-height="189" /></a></span></td></tr><tr><th scope="row" width="15%" style="background-color:light-dark(#c3fdb8, #003500) !important;color:inherit"><a href="/wiki/Chromosome" title="Chromosome">Chr.</a></th><td colspan="3" width="85%" style="background-color:light-dark(#eee, #27292d) !important;color:inherit"><span class="plainlinks"><a href="/wiki/Chromosome_2_(human)" class="mw-redirect" title="Chromosome 2 (human)">Chromosome 2 (human)</a><sup id="cite_ref-refGRCh38Ensembl_1-0" class="reference"><a href="#cite_note-refGRCh38Ensembl-1"><span class="cite-bracket">[</span>1<span class="cite-bracket">]</span></a></sup></span></td></tr><tr><td colspan="4" style="text-align:center;background-color:light-dark(#eee, #27292d) !important;color:inherit"><div align="center"><div style="position: relative; width: 300px;"><span typeof="mw:File"><a href="/wiki/File:Human_chromosome_2_ideogram.svg" class="mw-file-description" title="Chromosome 2 (human)"><img alt="Chromosome 2 (human)" src="//upload.wikimedia.org/wikipedia/commons/thumb/7/77/Human_chromosome_2_ideogram.svg/300px-Human_chromosome_2_ideogram.svg.png" decoding="async" width="300" height="58" class="mw-file-element" srcset="//upload.wikimedia.org/wikipedia/commons/thumb/7/77/Human_chromosome_2_ideogram.svg/450px-Human_chromosome_2_ideogram.svg.png 1.5x, //upload.wikimedia.org/wikipedia/commons/thumb/7/77/Human_chromosome_2_ideogram.svg/600px-Human_chromosome_2_ideogram.svg.png 2x" data-file-width="1125" data-file-height="216" /></a></span><div style="position: absolute; left: 288.32132965045px; top: 2px; padding: 0;"><span typeof="mw:File"><a href="/wiki/File:HSR_1996_II_3.5e.svg" class="mw-file-description" title="Genomic location for PDCD1"><img alt="Genomic location for PDCD1" src="//upload.wikimedia.org/wikipedia/commons/thumb/d/d8/HSR_1996_II_3.5e.svg/14px-HSR_1996_II_3.5e.svg.png" decoding="async" width="14" height="14" class="mw-file-element" srcset="//upload.wikimedia.org/wikipedia/commons/thumb/d/d8/HSR_1996_II_3.5e.svg/21px-HSR_1996_II_3.5e.svg.png 1.5x, //upload.wikimedia.org/wikipedia/commons/thumb/d/d8/HSR_1996_II_3.5e.svg/28px-HSR_1996_II_3.5e.svg.png 2x" data-file-width="142" data-file-height="142" /></a></span></div><div style="position: absolute; left: 294.3px; top: 19px; padding: 0;"><span typeof="mw:File"><a href="/wiki/File:Red_rectangle_2x18.png" class="mw-file-description" title="Genomic location for PDCD1"><img alt="Genomic location for PDCD1" src="//upload.wikimedia.org/wikipedia/commons/6/6a/Red_rectangle_2x18.png" decoding="async" width="2" height="18" class="mw-file-element" data-file-width="2" data-file-height="18" /></a></span></div></div></div></td></tr><tr><th scope="row" rowspan="2" width="15%" style="background-color:light-dark(#c3fdb8, #003500) !important;color:inherit"><a href="/wiki/Locus_(genetics)" title="Locus (genetics)">Band</a></th><td rowspan="2" width="35%" style="background-color:light-dark(#eee, #27292d) !important;color:inherit"><span class="plainlinks">2q37.3</span></td><th scope="row" style="background-color:light-dark(#c3fdb8, #003500) !important;color:inherit">Start</th><td style="background-color:light-dark(#eee, #27292d) !important;color:inherit"><span class="plainlinks">241,849,884 <a href="/wiki/Base_pair" title="Base pair">bp</a><sup id="cite_ref-refGRCh38Ensembl_1-1" class="reference"><a href="#cite_note-refGRCh38Ensembl-1"><span class="cite-bracket">[</span>1<span class="cite-bracket">]</span></a></sup></span></td></tr><tr><th scope="row" style="background-color:light-dark(#c3fdb8, #003500) !important;color:inherit">End</th><td style="background-color:light-dark(#eee, #27292d) !important;color:inherit"><span class="plainlinks">241,858,894 <a href="/wiki/Base_pair" title="Base pair">bp</a><sup id="cite_ref-refGRCh38Ensembl_1-2" class="reference"><a href="#cite_note-refGRCh38Ensembl-1"><span class="cite-bracket">[</span>1<span class="cite-bracket">]</span></a></sup></span></td></tr></tbody></table></td></tr><tr><td colspan="4" style="text-align:center;background-color:light-dark(#eee, #27292d) !important;color:inherit"><table class="collapsible collapsed" style="padding:0;border:none;margin:0;width:100%;text-align:left"><tbody><tr><th colspan="4" style="text-align:center;background-color:light-dark(#ddd, #404244) !important;color:inherit">Gene location (<a href="/wiki/Laboratory_mouse" title="Laboratory mouse">Mouse</a>)</th></tr><tr><td colspan="4" style="text-align:center;background-color:light-dark(#eee, #27292d) !important;color:inherit"><span typeof="mw:File"><a href="/wiki/File:Ideogram_house_mouse_chromosome_1.svg" class="mw-file-description" title="Chromosome 1 (mouse)"><img alt="Chromosome 1 (mouse)" src="//upload.wikimedia.org/wikipedia/commons/thumb/f/fb/Ideogram_house_mouse_chromosome_1.svg/330px-Ideogram_house_mouse_chromosome_1.svg.png" decoding="async" width="260" height="111" class="mw-file-element" srcset="//upload.wikimedia.org/wikipedia/commons/thumb/f/fb/Ideogram_house_mouse_chromosome_1.svg/390px-Ideogram_house_mouse_chromosome_1.svg.png 1.5x, //upload.wikimedia.org/wikipedia/commons/thumb/f/fb/Ideogram_house_mouse_chromosome_1.svg/520px-Ideogram_house_mouse_chromosome_1.svg.png 2x" data-file-width="470" data-file-height="200" /></a></span></td></tr><tr><th scope="row" width="15%" style="background-color:light-dark(#c3fdb8, #003500) !important;color:inherit"><a href="/wiki/Chromosome" title="Chromosome">Chr.</a></th><td colspan="3" width="85%" style="background-color:light-dark(#eee, #27292d) !important;color:inherit"><span class="plainlinks">Chromosome 1 (mouse)<sup id="cite_ref-refGRCm38Ensembl_2-0" class="reference"><a href="#cite_note-refGRCm38Ensembl-2"><span class="cite-bracket">[</span>2<span class="cite-bracket">]</span></a></sup></span></td></tr><tr><td colspan="4" style="text-align:center;background-color:light-dark(#eee, #27292d) !important;color:inherit"><div align="center"><div style="position: relative; width: 300px;"><span typeof="mw:File"><a href="/wiki/File:Ideogram_of_house_mouse_chromosome_1.svg" class="mw-file-description" title="Chromosome 1 (mouse)"><img alt="Chromosome 1 (mouse)" src="//upload.wikimedia.org/wikipedia/commons/thumb/5/5b/Ideogram_of_house_mouse_chromosome_1.svg/300px-Ideogram_of_house_mouse_chromosome_1.svg.png" decoding="async" width="300" height="58" class="mw-file-element" srcset="//upload.wikimedia.org/wikipedia/commons/thumb/5/5b/Ideogram_of_house_mouse_chromosome_1.svg/450px-Ideogram_of_house_mouse_chromosome_1.svg.png 1.5x, //upload.wikimedia.org/wikipedia/commons/thumb/5/5b/Ideogram_of_house_mouse_chromosome_1.svg/600px-Ideogram_of_house_mouse_chromosome_1.svg.png 2x" data-file-width="1200" data-file-height="231" /></a></span><div style="position: absolute; left: 136.00453957418px; top: 2px; padding: 0;"><span typeof="mw:File"><a href="/wiki/File:HSR_1996_II_3.5e.svg" class="mw-file-description" title="Genomic location for PDCD1"><img alt="Genomic location for PDCD1" src="//upload.wikimedia.org/wikipedia/commons/thumb/d/d8/HSR_1996_II_3.5e.svg/14px-HSR_1996_II_3.5e.svg.png" decoding="async" width="14" height="14" class="mw-file-element" srcset="//upload.wikimedia.org/wikipedia/commons/thumb/d/d8/HSR_1996_II_3.5e.svg/21px-HSR_1996_II_3.5e.svg.png 1.5x, //upload.wikimedia.org/wikipedia/commons/thumb/d/d8/HSR_1996_II_3.5e.svg/28px-HSR_1996_II_3.5e.svg.png 2x" data-file-width="142" data-file-height="142" /></a></span></div><div style="position: absolute; left: 142px; top: 19px; padding: 0;"><span typeof="mw:File"><a href="/wiki/File:Red_rectangle_2x18.png" class="mw-file-description" title="Genomic location for PDCD1"><img alt="Genomic location for PDCD1" src="//upload.wikimedia.org/wikipedia/commons/6/6a/Red_rectangle_2x18.png" decoding="async" width="2" height="18" class="mw-file-element" data-file-width="2" data-file-height="18" /></a></span></div></div></div></td></tr><tr><th scope="row" rowspan="2" width="15%" style="background-color:light-dark(#c3fdb8, #003500) !important;color:inherit"><a href="/wiki/Locus_(genetics)" title="Locus (genetics)">Band</a></th><td rowspan="2" width="35%" style="background-color:light-dark(#eee, #27292d) !important;color:inherit"><span class="plainlinks">1|1 D</span></td><th scope="row" style="background-color:light-dark(#c3fdb8, #003500) !important;color:inherit">Start</th><td style="background-color:light-dark(#eee, #27292d) !important;color:inherit"><span class="plainlinks">93,966,027 <a href="/wiki/Base_pair" title="Base pair">bp</a><sup id="cite_ref-refGRCm38Ensembl_2-1" class="reference"><a href="#cite_note-refGRCm38Ensembl-2"><span class="cite-bracket">[</span>2<span class="cite-bracket">]</span></a></sup></span></td></tr><tr><th scope="row" style="background-color:light-dark(#c3fdb8, #003500) !important;color:inherit">End</th><td style="background-color:light-dark(#eee, #27292d) !important;color:inherit"><span class="plainlinks">93,980,278 <a href="/wiki/Base_pair" title="Base pair">bp</a><sup id="cite_ref-refGRCm38Ensembl_2-2" class="reference"><a href="#cite_note-refGRCm38Ensembl-2"><span class="cite-bracket">[</span>2<span class="cite-bracket">]</span></a></sup></span></td></tr></tbody></table></td></tr><tr><td colspan="4" style="text-align:center;background-color:light-dark(#eee, #27292d) !important;color:inherit"><table class="collapsible collapsed" style="padding:0;border:none;margin:0;width:100%;text-align:left"><tbody><tr><th colspan="4" style="text-align:center;background-color:light-dark(#ddd, #404244) !important;color:inherit"><a href="/wiki/Gene_expression" title="Gene expression">RNA expression</a> pattern</th></tr><tr><th scope="row" style="background-color:light-dark(#c3fdb8, #003500) !important;color:inherit"><a rel="nofollow" class="external text" href="https://www.bgee.org/">Bgee</a></th><td><table class="none" style="padding:0;border:none;margin:0;width:100%;text-align:left"><tbody><tr><th><b><a href="/wiki/Human_genome" title="Human genome">Human</a></b></th><th><b><a href="/wiki/Laboratory_mouse" title="Laboratory mouse">Mouse</a> (ortholog)</b></th></tr><tr><td><table class="none" style="padding:0;border:none;margin:0;width:100%;text-align:center"><tbody><tr><td colspan="1"><span class="plainlinks" style="margin:-3px"><a rel="nofollow" class="external text" href="https://www.bgee.org/gene/ENSG00000188389">Top expressed in</a></span></td></tr><tr><td colspan="1"><div class="plainlinks" style="margin:-12px 0px -10px 0px"><ul style="line-height:15%;margin:9px"><li style="line-height: 137%;">lymph node</li><br /><li style="line-height: 137%;">granulocyte</li><br /><li style="line-height: 137%;">spleen</li><br /><li style="line-height: 137%;">right auricle of heart</li><br /><li style="line-height: 137%;">appendix</li><br /><li style="line-height: 137%;">blood</li><br /><li style="line-height: 137%;">left ventricle</li><br /><li style="line-height: 137%;">mucosa of transverse colon</li><br /><li style="line-height: 137%;">upper lobe of left lung</li><br /><li style="line-height: 137%;">tonsil</li></ul></div></td></tr></tbody></table></td><td><table class="none" style="padding:0;border:none;margin:0;width:100%;text-align:center"><tbody><tr><td colspan="1"><span class="plainlinks" style="margin:-3px"><a rel="nofollow" class="external text" href="https://www.bgee.org/gene/ENSMUSG00000026285">Top expressed in</a></span></td></tr><tr><td colspan="1"><div class="plainlinks" style="margin:-12px 0px -10px 0px"><ul style="line-height:15%;margin:9px"><li style="line-height: 137%;">embryo</li><br /><li style="line-height: 137%;">thymus</li><br /><li style="line-height: 137%;">embryo</li><br /><li style="line-height: 137%;">mesenteric lymph nodes</li><br /><li style="line-height: 137%;">zygote</li><br /><li style="line-height: 137%;">cumulus cell</li><br /><li style="line-height: 137%;">primary oocyte</li><br /><li style="line-height: 137%;">spleen</li><br /><li style="line-height: 137%;">blood</li><br /><li style="line-height: 137%;">ovary</li></ul></div></td></tr></tbody></table></td></tr><tr><td colspan="4" style="text-align:center;background-color:light-dark(#eee, #27292d) !important;color:inherit"><span class="plainlinks"><a rel="nofollow" class="external text" href="https://www.bgee.org/gene/ENSG00000188389">More reference expression data</a></span></td></tr></tbody></table></td></tr><tr><th scope="row" style="background-color:light-dark(#c3fdb8, #003500) !important;color:inherit"><a rel="nofollow" class="external text" href="http://biogps.org/">BioGPS</a></th><td><table class="none" style="padding:0;border:none;margin:0;width:100%;text-align:left"><tbody><tr><td colspan="4" style="text-align:center;background-color:light-dark(#eee, #27292d) !important;color:inherit"><span typeof="mw:File"><a href="/wiki/File:PBB_GE_PDCD1_207634_at_fs.png" class="mw-file-description"><img src="//upload.wikimedia.org/wikipedia/commons/thumb/d/da/PBB_GE_PDCD1_207634_at_fs.png/250px-PBB_GE_PDCD1_207634_at_fs.png" decoding="async" width="250" height="181" class="mw-file-element" srcset="//upload.wikimedia.org/wikipedia/commons/thumb/d/da/PBB_GE_PDCD1_207634_at_fs.png/500px-PBB_GE_PDCD1_207634_at_fs.png 1.5x" data-file-width="732" data-file-height="530" /></a></span></td></tr><tr><td colspan="4" style="text-align:center;background-color:light-dark(#eee, #27292d) !important;color:inherit"><span class="plainlinks"><a rel="nofollow" class="external text" href="http://biogps.org/gene/5133/">More reference expression data</a></span></td></tr></tbody></table></td></tr></tbody></table></td></tr><tr><td colspan="4" style="text-align:center;background-color:light-dark(#eee, #27292d) !important;color:inherit"><table class="collapsible collapsed" style="padding:0;border:none;margin:0;width:100%;text-align:left"><tbody><tr><th colspan="4" style="text-align:center;background-color:light-dark(#ddd, #404244) !important;color:inherit"><a href="/wiki/Gene_ontology" class="mw-redirect" title="Gene ontology">Gene ontology</a></th></tr><tr><td style="background-color:light-dark(#c3fdb8, #003500) !important;color:inherit;font-weight:bold">Molecular function</td><td style="background-color:light-dark(#eee, #27292d) !important;color:inherit"><div class="plainlinks"> <ul><li><a rel="nofollow" class="external text" href="http://amigo.geneontology.org/amigo/term/GO:0005515">protein binding</a></li> <li><a rel="nofollow" class="external text" href="http://amigo.geneontology.org/amigo/term/">signal transducer activity</a></li></ul> </div></td></tr><tr><td style="background-color:light-dark(#c3fdb8, #003500) !important;color:inherit;font-weight:bold">Cellular component</td><td style="background-color:light-dark(#eee, #27292d) !important;color:inherit"><div class="plainlinks"> <ul><li><a rel="nofollow" class="external text" href="http://amigo.geneontology.org/amigo/term/GO:0016021">integral component of membrane</a></li> <li><a rel="nofollow" class="external text" href="http://amigo.geneontology.org/amigo/term/GO:0005886">plasma membrane</a></li> <li><a rel="nofollow" class="external text" href="http://amigo.geneontology.org/amigo/term/GO:0016020">membrane</a></li> <li><a rel="nofollow" class="external text" href="http://amigo.geneontology.org/amigo/term/GO:0009897">external side of plasma membrane</a></li></ul> </div></td></tr><tr><td style="background-color:light-dark(#c3fdb8, #003500) !important;color:inherit;font-weight:bold">Biological process</td><td style="background-color:light-dark(#eee, #27292d) !important;color:inherit"><div class="plainlinks"> <ul><li><a rel="nofollow" class="external text" href="http://amigo.geneontology.org/amigo/term/GO:0043065">positive regulation of apoptotic process</a></li> <li><a rel="nofollow" class="external text" href="http://amigo.geneontology.org/amigo/term/GO:0007275">multicellular organism development</a></li> <li><a rel="nofollow" class="external text" href="http://amigo.geneontology.org/amigo/term/GO:0031295">T cell costimulation</a></li> <li><a rel="nofollow" class="external text" href="http://amigo.geneontology.org/amigo/term/GO:0043066">negative regulation of apoptotic process</a></li> <li><a rel="nofollow" class="external text" href="http://amigo.geneontology.org/amigo/term/GO:0070234">positive regulation of T cell apoptotic process</a></li> <li><a rel="nofollow" class="external text" href="http://amigo.geneontology.org/amigo/term/GO:0006959">humoral immune response</a></li> <li><a rel="nofollow" class="external text" href="http://amigo.geneontology.org/amigo/term/GO:0002644">negative regulation of tolerance induction</a></li> <li><a rel="nofollow" class="external text" href="http://amigo.geneontology.org/amigo/term/GO:0002376">immune system process</a></li> <li><a rel="nofollow" class="external text" href="http://amigo.geneontology.org/amigo/term/GO:0006915">apoptotic process</a></li> <li><a rel="nofollow" class="external text" href="http://amigo.geneontology.org/amigo/term/GO:0007165">signal transduction</a></li></ul> </div></td></tr><tr><td colspan="4" style="background-color:light-dark(#eee, #27292d) !important;color:inherit;text-align:center">Sources:<a rel="nofollow" class="external text" href="http://amigo.geneontology.org/">Amigo</a> / <a rel="nofollow" class="external text" href="https://www.ebi.ac.uk/QuickGO/">QuickGO</a></td></tr></tbody></table></td></tr><tr><td colspan="4" style="text-align:center;background-color:light-dark(#eee, #27292d) !important;color:inherit"><table class="collapsible" style="padding:0;border:none;margin:0;width:100%;text-align:left"><tbody><tr><th colspan="4" style="text-align:center;background-color:light-dark(#ddd, #404244) !important;color:inherit"><a href="/wiki/Orthologs" class="mw-redirect" title="Orthologs">Orthologs</a></th></tr><tr><th scope="row" style="background-color:light-dark(#c3fdb8, #003500) !important;color:inherit">Species</th><td><b>Human</b></td><td><b>Mouse</b></td></tr><tr><th scope="row" style="background-color:light-dark(#c3fdb8, #003500) !important;color:inherit"><a href="/wiki/Entrez" title="Entrez">Entrez</a></th><td><table class="none" style="padding:0;border:none;margin:0;width:100%;text-align:right"><tbody><tr><th colspan="1"><span class="plainlinks"></span></th></tr><tr><td colspan="1"><p class="plainlinks"><a rel="nofollow" class="external text" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=gene&cmd=retrieve&dopt=default&list_uids=5133&rn=1">5133</a></p></td></tr></tbody></table></td><td><table class="none" style="padding:0;border:none;margin:0;width:100%;text-align:right"><tbody><tr><th colspan="1"><span class="plainlinks"></span></th></tr><tr><td colspan="1"><p class="plainlinks"><a rel="nofollow" class="external text" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=gene&cmd=retrieve&dopt=default&list_uids=18566&rn=1">18566</a></p></td></tr></tbody></table></td></tr><tr><th scope="row" style="background-color:light-dark(#c3fdb8, #003500) !important;color:inherit"><a href="/wiki/Ensembl" class="mw-redirect" title="Ensembl">Ensembl</a></th><td><table class="none" style="padding:0;border:none;margin:0;width:100%;text-align:right"><tbody><tr><th colspan="1"><span class="plainlinks"></span></th></tr><tr><td colspan="1"><p class="plainlinks"><a rel="nofollow" class="external text" href="http://www.ensembl.org/Homo_sapiens/geneview?gene=ENSG00000188389;db=core">ENSG00000188389</a><br /><a rel="nofollow" class="external text" href="http://www.ensembl.org/Homo_sapiens/geneview?gene=ENSG00000276977;db=core">ENSG00000276977</a></p></td></tr></tbody></table></td><td><table class="none" style="padding:0;border:none;margin:0;width:100%;text-align:right"><tbody><tr><th colspan="1"><span class="plainlinks"></span></th></tr><tr><td colspan="1"><p class="plainlinks"><a rel="nofollow" class="external text" href="http://www.ensembl.org/Mus_musculus/geneview?gene=ENSMUSG00000026285;db=core">ENSMUSG00000026285</a></p></td></tr></tbody></table></td></tr><tr><th scope="row" style="background-color:light-dark(#c3fdb8, #003500) !important;color:inherit"><a href="/wiki/UniProt" title="UniProt">UniProt</a></th><td><table class="none" style="padding:0;border:none;margin:0;width:100%;text-align:right"><tbody><tr><th colspan="1"><span class="plainlinks"></span></th></tr><tr><td colspan="1"><p class="plainlinks"><a rel="nofollow" class="external text" href="https://www.uniprot.org/uniprot/Q15116">Q15116</a></p></td></tr></tbody></table></td><td><table class="none" style="padding:0;border:none;margin:0;width:100%;text-align:right"><tbody><tr><th colspan="1"><span class="plainlinks"></span></th></tr><tr><td colspan="1"><p class="plainlinks"><a rel="nofollow" class="external text" href="https://www.uniprot.org/uniprot/Q02242">Q02242</a></p></td></tr></tbody></table></td></tr><tr><th scope="row" style="background-color:light-dark(#c3fdb8, #003500) !important;color:inherit">RefSeq (mRNA)</th><td><table class="none" style="padding:0;border:none;margin:0;width:100%;text-align:right"><tbody><tr><th colspan="1" class="plainlinks"></th></tr><tr><td colspan="1"><p><span class="plainlinks"><a rel="nofollow" class="external text" href="https://www.ncbi.nlm.nih.gov/entrez/viewer.fcgi?val=NM_005018">NM_005018</a></span></p></td></tr></tbody></table></td><td><table class="none" style="padding:0;border:none;margin:0;width:100%;text-align:right"><tbody><tr><th colspan="1" class="plainlinks"></th></tr><tr><td colspan="1"><p><span class="plainlinks"><a rel="nofollow" class="external text" href="https://www.ncbi.nlm.nih.gov/entrez/viewer.fcgi?val=NM_008798">NM_008798</a></span></p></td></tr></tbody></table></td></tr><tr><th scope="row" style="background-color:light-dark(#c3fdb8, #003500) !important;color:inherit">RefSeq (protein)</th><td><table class="none" style="padding:0;border:none;margin:0;width:100%;text-align:right"><tbody><tr><th colspan="1" class="plainlinks"></th></tr><tr><td colspan="1"><p><span class="plainlinks"><a rel="nofollow" class="external text" href="https://www.ncbi.nlm.nih.gov/entrez/viewer.fcgi?val=NP_005009">NP_005009</a></span></p></td></tr></tbody></table></td><td><table class="none" style="padding:0;border:none;margin:0;width:100%;text-align:right"><tbody><tr><th colspan="1" class="plainlinks"></th></tr><tr><td colspan="1"><p><span class="plainlinks"><a rel="nofollow" class="external text" href="https://www.ncbi.nlm.nih.gov/entrez/viewer.fcgi?val=NP_032824">NP_032824</a></span></p></td></tr></tbody></table></td></tr><tr><th scope="row" style="background-color:light-dark(#c3fdb8, #003500) !important;color:inherit">Location (UCSC)</th><td><span class="plainlinks"><a rel="nofollow" class="external text" href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&position=chr2:241849884-241858894">Chr 2: 241.85 – 241.86 Mb</a></span></td><td><span class="plainlinks"><a rel="nofollow" class="external text" href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Mouse&db=mm0&position=chr1:93966027-93980278">Chr 1: 93.97 – 93.98 Mb</a></span></td></tr><tr><th scope="row" style="background-color:light-dark(#c3fdb8, #003500) !important;color:inherit"><a href="/wiki/PubMed" title="PubMed">PubMed</a> search</th><td><span class="plainlinks"><sup id="cite_ref-3" class="reference"><a href="#cite_note-3"><span class="cite-bracket">[</span>3<span class="cite-bracket">]</span></a></sup></span></td><td><span class="plainlinks"><sup id="cite_ref-4" class="reference"><a href="#cite_note-4"><span class="cite-bracket">[</span>4<span class="cite-bracket">]</span></a></sup></span></td></tr></tbody></table></td></tr><tr><td colspan="4" style="text-align:center;background-color:light-dark(#eee, #27292d) !important;color:inherit"><a href="/wiki/Wikidata" title="Wikidata">Wikidata</a></td></tr><tr><td colspan="4" style="text-align:center;background-color:light-dark(#eee, #27292d) !important;color:inherit"><table style="padding:0;border:none;margin:0;width:100%;text-align:center"><tbody><tr><td colspan="2" style="background-color:light-dark(#eee, #27292d) !important;color:inherit;text-align:center"><a href="https://www.wikidata.org/wiki/Q18030399" class="extiw" title="d:Q18030399">View/Edit Human</a></td><td colspan="2" style="background-color:light-dark(#eee, #27292d) !important;color:inherit;text-align:center"><a href="https://www.wikidata.org/wiki/Q18252933" class="extiw" title="d:Q18252933">View/Edit Mouse</a></td></tr></tbody></table></td></tr></tbody></table> <p><b>Programmed cell death protein 1</b> <b>(PD-1)</b>, (<b>CD279</b> <a href="/wiki/Cluster_of_differentiation" title="Cluster of differentiation">cluster of differentiation</a> 279). PD-1 is a <a href="/wiki/Protein" title="Protein">protein</a> encoded in humans by the <i>PDCD1</i> <a href="/wiki/Gene" title="Gene">gene</a>.<sup id="cite_ref-pmid7851902_5-0" class="reference"><a href="#cite_note-pmid7851902-5"><span class="cite-bracket">[</span>5<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-entrez_6-0" class="reference"><a href="#cite_note-entrez-6"><span class="cite-bracket">[</span>6<span class="cite-bracket">]</span></a></sup> PD-1 is a <a href="/wiki/Cell_surface_receptor" title="Cell surface receptor">cell surface receptor</a> on <a href="/wiki/T_cell" title="T cell">T cells</a> and <a href="/wiki/B_cell" title="B cell">B cells</a> that has a role in regulating the <a href="/wiki/Immune_system" title="Immune system">immune system</a>'s response to the cells of the human body by down-regulating the immune system and promoting self-tolerance by suppressing <a href="/wiki/T_cell" title="T cell">T cell</a> inflammatory activity. This prevents <a href="/wiki/Autoimmune_diseases" class="mw-redirect" title="Autoimmune diseases">autoimmune diseases</a>, but it can also prevent the immune system from killing cancer cells.<sup id="cite_ref-:1_7-0" class="reference"><a href="#cite_note-:1-7"><span class="cite-bracket">[</span>7<span class="cite-bracket">]</span></a></sup> </p><p>PD-1 is an <a href="/wiki/Immune_checkpoint" title="Immune checkpoint">immune checkpoint</a> and guards against autoimmunity through two mechanisms. First, it promotes <a href="/wiki/Apoptosis" title="Apoptosis">apoptosis</a> (programmed cell death) of <a href="/wiki/Antigen" title="Antigen">antigen</a>-specific T-cells in <a href="/wiki/Lymph_node" title="Lymph node">lymph nodes</a>. Second, it reduces apoptosis in <a href="/wiki/Regulatory_T_cell" title="Regulatory T cell">regulatory T cells</a> (anti-inflammatory, suppressive T cells).<sup id="cite_ref-pmid20636820_8-0" class="reference"><a href="#cite_note-pmid20636820-8"><span class="cite-bracket">[</span>8<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-pmid21276005_9-0" class="reference"><a href="#cite_note-pmid21276005-9"><span class="cite-bracket">[</span>9<span class="cite-bracket">]</span></a></sup> </p><p><a href="/wiki/PD-1_inhibitor" class="mw-redirect" title="PD-1 inhibitor">PD-1 inhibitors</a>, a new class of drugs that block PD-1, activate the immune system to attack tumors and are used to treat certain types of cancer.<sup id="cite_ref-:1_7-1" class="reference"><a href="#cite_note-:1-7"><span class="cite-bracket">[</span>7<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-bms_10-0" class="reference"><a href="#cite_note-bms-10"><span class="cite-bracket">[</span>10<span class="cite-bracket">]</span></a></sup> </p><p>PD-1 is a cell surface receptor that belongs to the <a href="/wiki/Immunoglobulin_superfamily" title="Immunoglobulin superfamily">immunoglobulin superfamily</a> and is expressed on T cells and <a href="/wiki/Pro-B_cell" class="mw-redirect" title="Pro-B cell">pro-B cells</a>.<sup id="cite_ref-entrez_6-1" class="reference"><a href="#cite_note-entrez-6"><span class="cite-bracket">[</span>6<span class="cite-bracket">]</span></a></sup> PD-1 binds two <a href="/wiki/Ligand_(biochemistry)" title="Ligand (biochemistry)">ligands</a>, <a href="/wiki/PD-L1" title="PD-L1">PD-L1</a> and <a href="/wiki/CD273" class="mw-redirect" title="CD273">PD-L2</a>. </p> <meta property="mw:PageProp/toc" /> <div class="mw-heading mw-heading2"><h2 id="Discovery">Discovery</h2><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Programmed_cell_death_protein_1&action=edit&section=1" title="Edit section: Discovery"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <p>In a screen for genes involved in <a href="/wiki/Apoptosis" title="Apoptosis">apoptosis</a>, Yasumasa Ishida, <a href="/wiki/Tasuku_Honjo" title="Tasuku Honjo">Tasuku Honjo</a> and colleagues at <a href="/wiki/Kyoto_University" title="Kyoto University">Kyoto University</a> in 1992 discovered and named PD-1.<sup id="cite_ref-Ishida_1992_11-0" class="reference"><a href="#cite_note-Ishida_1992-11"><span class="cite-bracket">[</span>11<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-Bardhan_2016_12-0" class="reference"><a href="#cite_note-Bardhan_2016-12"><span class="cite-bracket">[</span>12<span class="cite-bracket">]</span></a></sup> In 1999, the same group demonstrated that mice where PD-1 was knocked down were prone to autoimmune disease and hence concluded that PD-1 was a negative regulator of immune responses.<sup id="cite_ref-Bardhan_2016_12-1" class="reference"><a href="#cite_note-Bardhan_2016-12"><span class="cite-bracket">[</span>12<span class="cite-bracket">]</span></a></sup> </p> <div class="mw-heading mw-heading2"><h2 id="Structure">Structure</h2><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Programmed_cell_death_protein_1&action=edit&section=2" title="Edit section: Structure"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <p>PD-1 is a <a href="/wiki/Type_I_membrane_protein" class="mw-redirect" title="Type I membrane protein">type I membrane protein</a> of 288 <a href="/wiki/Amino_acid" title="Amino acid">amino acids</a>. PD-1 is a member of the extended <a href="/wiki/CD28" title="CD28">CD28</a>/<a href="/wiki/CTLA-4" class="mw-redirect" title="CTLA-4">CTLA-4</a> family of <a href="/wiki/T_cell" title="T cell">T cell</a> regulators.<sup id="cite_ref-Ishida_1992_11-1" class="reference"><a href="#cite_note-Ishida_1992-11"><span class="cite-bracket">[</span>11<span class="cite-bracket">]</span></a></sup> The protein's structure includes an extracellular <a href="/wiki/Immunoglobulin_superfamily#Classification" title="Immunoglobulin superfamily">IgV</a> domain followed by a <a href="/wiki/Transmembrane" class="mw-redirect" title="Transmembrane">transmembrane</a> region and an intracellular tail. The intracellular tail contains two <a href="/wiki/Phosphorylation" title="Phosphorylation">phosphorylation</a> sites located in an <a href="/wiki/Immunoreceptor_tyrosine-based_inhibitory_motif" title="Immunoreceptor tyrosine-based inhibitory motif">immunoreceptor tyrosine-based inhibitory motif</a> and an immunoreceptor tyrosine-based switch motif, which suggests that PD-1 negatively regulates T-cell receptor <a href="/wiki/T-cell_receptor" title="T-cell receptor">TCR</a> signals.<sup id="cite_ref-Ishida_1992_11-2" class="reference"><a href="#cite_note-Ishida_1992-11"><span class="cite-bracket">[</span>11<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-pmid17195077_13-0" class="reference"><a href="#cite_note-pmid17195077-13"><span class="cite-bracket">[</span>13<span class="cite-bracket">]</span></a></sup> This is consistent with binding of <a href="/wiki/PTPN6" title="PTPN6">SHP-1</a> and <a href="/wiki/PTPN11" title="PTPN11">SHP-2</a> <a href="/wiki/Protein_phosphatase" title="Protein phosphatase">phosphatases</a> to the cytoplasmic tail of PD-1 upon ligand binding. In addition, PD-1 ligation up-regulates <a href="/wiki/E3_ubiquitin_ligase" class="mw-redirect" title="E3 ubiquitin ligase">E3 ubiquitin ligases</a> <a href="/wiki/CBL_(gene)" title="CBL (gene)">CBL-b</a> and c-CBL that trigger T cell receptor down-modulation.<sup id="cite_ref-pmid21739608_14-0" class="reference"><a href="#cite_note-pmid21739608-14"><span class="cite-bracket">[</span>14<span class="cite-bracket">]</span></a></sup> PD-1 is expressed on the surface of activated T cells, <a href="/wiki/B_cell" title="B cell">B cells</a>, and <a href="/wiki/Macrophage" title="Macrophage">macrophages</a>,<sup id="cite_ref-pmid8671665_15-0" class="reference"><a href="#cite_note-pmid8671665-15"><span class="cite-bracket">[</span>15<span class="cite-bracket">]</span></a></sup> suggesting that compared to CTLA-4, PD-1 more broadly negatively regulates immune responses. </p> <div class="mw-heading mw-heading2"><h2 id="Ligands">Ligands</h2><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Programmed_cell_death_protein_1&action=edit&section=3" title="Edit section: Ligands"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <p>PD-1 has two <a href="/wiki/Ligand_(biochemistry)" title="Ligand (biochemistry)">ligands</a>, <a href="/wiki/PD-L1" title="PD-L1">PD-L1</a> and <a href="/wiki/CD273" class="mw-redirect" title="CD273">PD-L2</a>, which are members of the <a href="/wiki/B7_(protein)" title="B7 (protein)">B7</a> family.<sup id="cite_ref-Freeman_2000_16-0" class="reference"><a href="#cite_note-Freeman_2000-16"><span class="cite-bracket">[</span>16<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-Latchman_2001_17-0" class="reference"><a href="#cite_note-Latchman_2001-17"><span class="cite-bracket">[</span>17<span class="cite-bracket">]</span></a></sup> PD-L1 protein is upregulated on macrophages and <a href="/wiki/Dendritic_cell" title="Dendritic cell">dendritic cells</a> (DC) in response to <a href="/wiki/Lipopolysaccharide" title="Lipopolysaccharide">LPS</a> and <a href="/wiki/Granulocyte_macrophage_colony-stimulating_factor" class="mw-redirect" title="Granulocyte macrophage colony-stimulating factor">GM-CSF</a> treatment, and on T cells and B cells upon TCR and B cell receptor signaling, whereas in resting mice, PD-L1 <a href="/wiki/MRNA" class="mw-redirect" title="MRNA">mRNA</a> can be detected in the heart, lung, thymus, spleen, and kidney.<sup id="cite_ref-Freeman_2000_16-1" class="reference"><a href="#cite_note-Freeman_2000-16"><span class="cite-bracket">[</span>16<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-pmid12421930_18-0" class="reference"><a href="#cite_note-pmid12421930-18"><span class="cite-bracket">[</span>18<span class="cite-bracket">]</span></a></sup> PD-L1 is expressed on almost all murine tumor cell lines, including PA1 myeloma, P815 mastocytoma, and <a href="/wiki/B16_melanoma" title="B16 melanoma">B16 melanoma</a> upon treatment with <a href="/wiki/Interferon-gamma" class="mw-redirect" title="Interferon-gamma">IFN-γ</a>.<sup id="cite_ref-Iwai_2002_19-0" class="reference"><a href="#cite_note-Iwai_2002-19"><span class="cite-bracket">[</span>19<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-Blank_2004_20-0" class="reference"><a href="#cite_note-Blank_2004-20"><span class="cite-bracket">[</span>20<span class="cite-bracket">]</span></a></sup> PD-L2 expression is more restricted and is expressed mainly by DCs and a few tumor lines.<sup id="cite_ref-Latchman_2001_17-1" class="reference"><a href="#cite_note-Latchman_2001-17"><span class="cite-bracket">[</span>17<span class="cite-bracket">]</span></a></sup> </p> <div class="mw-heading mw-heading2"><h2 id="Function">Function</h2><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Programmed_cell_death_protein_1&action=edit&section=4" title="Edit section: Function"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <p>Several lines of evidence suggest that PD-1 and its ligands negatively regulate immune responses. PD-1 <a href="/wiki/Knockout_mice" class="mw-redirect" title="Knockout mice">knockout mice</a> have been shown to develop lupus-like <a href="/wiki/Glomerulonephritis" title="Glomerulonephritis">glomerulonephritis</a> and dilated <a href="/wiki/Cardiomyopathy" title="Cardiomyopathy">cardiomyopathy</a> on the C57BL/6 and BALB/c backgrounds, respectively.<sup id="cite_ref-pmid10485649_21-0" class="reference"><a href="#cite_note-pmid10485649-21"><span class="cite-bracket">[</span>21<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-pmid11209085_22-0" class="reference"><a href="#cite_note-pmid11209085-22"><span class="cite-bracket">[</span>22<span class="cite-bracket">]</span></a></sup> In vitro, treatment of anti-<a href="/wiki/CD3_(immunology)" title="CD3 (immunology)">CD3</a> stimulated T cells with PD-L1-Ig results in reduced T cell proliferation and IFN-γ secretion.<sup id="cite_ref-Freeman_2000_16-2" class="reference"><a href="#cite_note-Freeman_2000-16"><span class="cite-bracket">[</span>16<span class="cite-bracket">]</span></a></sup> IFN-γ is a key pro-inflammatory cytokine that promotes T cell inflammatory activity. Reduced T cell proliferation was also correlated with attenuated IL-2 secretion and together, these data suggest that PD-1 negatively regulates T cell responses.<sup id="cite_ref-pmid11857337_23-0" class="reference"><a href="#cite_note-pmid11857337-23"><span class="cite-bracket">[</span>23<span class="cite-bracket">]</span></a></sup> </p><p>Experiments using PD-L1 transfected DCs and PD-1 expressing transgenic (Tg) <a href="/wiki/T_helper_cell" title="T helper cell">CD4<sup>+</sup></a> and <a href="/wiki/Cytotoxic_T_cell" title="Cytotoxic T cell">CD8<sup>+</sup></a> T cells suggest that CD8<sup>+</sup> T cells are more susceptible to inhibition by PD-L1, although this could be dependent on the strength of TCR signaling. Consistent with a role in negatively regulating CD8<sup>+</sup> T cell responses, using an <a href="/wiki/LCMV" class="mw-redirect" title="LCMV">LCMV</a> viral vector model of chronic infection, Rafi Ahmed's group showed that the PD-1-PD-L1 interaction inhibits activation, expansion and acquisition of effector functions of virus specific CD8<sup>+</sup> T cells, which can be reversed by blocking the PD-1-PD-L1 interaction.<sup id="cite_ref-pmid16382236_24-0" class="reference"><a href="#cite_note-pmid16382236-24"><span class="cite-bracket">[</span>24<span class="cite-bracket">]</span></a></sup> </p><p>Expression of PD-L1 on tumor cells inhibits anti-tumor activity through engagement of PD-1 on effector T cells.<sup id="cite_ref-Iwai_2002_19-1" class="reference"><a href="#cite_note-Iwai_2002-19"><span class="cite-bracket">[</span>19<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-Blank_2004_20-1" class="reference"><a href="#cite_note-Blank_2004-20"><span class="cite-bracket">[</span>20<span class="cite-bracket">]</span></a></sup> Expression of PD-L1 on tumors is correlated with reduced survival in esophageal, pancreatic and other types of cancers, highlighting this pathway as a target for immunotherapy.<sup id="cite_ref-:1_7-2" class="reference"><a href="#cite_note-:1-7"><span class="cite-bracket">[</span>7<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-pmid15837746_25-0" class="reference"><a href="#cite_note-pmid15837746-25"><span class="cite-bracket">[</span>25<span class="cite-bracket">]</span></a></sup> Triggering PD-1, expressed on monocytes and up-regulated upon monocytes activation, by its ligand PD-L1 induces IL-10 production which inhibits CD4 T-cell function.<sup id="cite_ref-pmid20208540_26-0" class="reference"><a href="#cite_note-pmid20208540-26"><span class="cite-bracket">[</span>26<span class="cite-bracket">]</span></a></sup> </p><p>In mice, expression of this gene is induced in the thymus when anti-CD3 antibodies are injected and large numbers of <a href="/wiki/Thymocyte" title="Thymocyte">thymocytes</a> undergo <a href="/wiki/Apoptosis" title="Apoptosis">apoptosis</a>. Mice deficient for this gene bred on a BALB/c background developed <a href="/wiki/Dilated_cardiomyopathy" title="Dilated cardiomyopathy">dilated cardiomyopathy</a> and died from <a href="/wiki/Congestive_heart_failure" class="mw-redirect" title="Congestive heart failure">congestive heart failure</a>. These studies suggest that this gene product may also be important in <a href="/wiki/T_cell" title="T cell">T cell</a> function and contribute to the prevention of <a href="/wiki/Autoimmune_disease" title="Autoimmune disease">autoimmune diseases</a>.<sup id="cite_ref-entrez_6-2" class="reference"><a href="#cite_note-entrez-6"><span class="cite-bracket">[</span>6<span class="cite-bracket">]</span></a></sup> </p><p>Overexpression of PD1 on CD8+ T cells is one of the indicators of <a href="/wiki/T-cell_exhaustion" class="mw-redirect" title="T-cell exhaustion">T-cell exhaustion</a> (e.g. in chronic infection or cancer).<sup id="cite_ref-:1_7-3" class="reference"><a href="#cite_note-:1-7"><span class="cite-bracket">[</span>7<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-Pauken2015_27-0" class="reference"><a href="#cite_note-Pauken2015-27"><span class="cite-bracket">[</span>27<span class="cite-bracket">]</span></a></sup> </p> <div class="mw-heading mw-heading2"><h2 id="Clinical_significance">Clinical significance</h2><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Programmed_cell_death_protein_1&action=edit&section=5" title="Edit section: Clinical significance"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <div class="mw-heading mw-heading3"><h3 id="Cancer">Cancer</h3><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Programmed_cell_death_protein_1&action=edit&section=6" title="Edit section: Cancer"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <figure class="mw-default-size" typeof="mw:File/Thumb"><a href="/wiki/File:Negative,_low_and_high_PD-L1_expression_by_immunohistochemistry.png" class="mw-file-description"><img src="//upload.wikimedia.org/wikipedia/commons/thumb/d/da/Negative%2C_low_and_high_PD-L1_expression_by_immunohistochemistry.png/220px-Negative%2C_low_and_high_PD-L1_expression_by_immunohistochemistry.png" decoding="async" width="220" height="88" class="mw-file-element" srcset="//upload.wikimedia.org/wikipedia/commons/thumb/d/da/Negative%2C_low_and_high_PD-L1_expression_by_immunohistochemistry.png/330px-Negative%2C_low_and_high_PD-L1_expression_by_immunohistochemistry.png 1.5x, //upload.wikimedia.org/wikipedia/commons/thumb/d/da/Negative%2C_low_and_high_PD-L1_expression_by_immunohistochemistry.png/440px-Negative%2C_low_and_high_PD-L1_expression_by_immunohistochemistry.png 2x" data-file-width="2000" data-file-height="804" /></a><figcaption>PD-L1 expression by chromogenic <a href="/wiki/Immunohistochemistry" title="Immunohistochemistry">immunohistochemistry</a> in cases of head and neck <a href="/wiki/Squamous_cell_carcinoma" class="mw-redirect" title="Squamous cell carcinoma">squamous cell carcinoma</a>, demonstrating negative (A), low (B), and high (C) PD-L1 protein levels<sup id="cite_ref-Müller_2017_28-0" class="reference"><a href="#cite_note-Müller_2017-28"><span class="cite-bracket">[</span>28<span class="cite-bracket">]</span></a></sup></figcaption></figure> <p>PD-L1, the ligand for PD1, is highly expressed in several cancers and hence the role of PD1 in cancer immune evasion is well established.<sup id="cite_ref-pmid27574444_29-0" class="reference"><a href="#cite_note-pmid27574444-29"><span class="cite-bracket">[</span>29<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-pmid26895815_30-0" class="reference"><a href="#cite_note-pmid26895815-30"><span class="cite-bracket">[</span>30<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-:1_7-4" class="reference"><a href="#cite_note-:1-7"><span class="cite-bracket">[</span>7<span class="cite-bracket">]</span></a></sup> <a href="/wiki/Monoclonal_antibodies" class="mw-redirect" title="Monoclonal antibodies">Monoclonal antibodies</a> targeting PD-1 that boost the <a href="/wiki/Immune_system" title="Immune system">immune system</a> are being developed for the treatment of <a href="/wiki/Cancer" title="Cancer">cancer</a>.<sup id="cite_ref-:1_7-5" class="reference"><a href="#cite_note-:1-7"><span class="cite-bracket">[</span>7<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-pmid21074057_31-0" class="reference"><a href="#cite_note-pmid21074057-31"><span class="cite-bracket">[</span>31<span class="cite-bracket">]</span></a></sup> Many tumor cells express PD-L1, an immunosuppressive PD-1 ligand; inhibition of the interaction between PD-1 and PD-L1 can enhance T-cell responses <i>in vitro</i> and mediate preclinical antitumor activity. This is known as <a href="/wiki/Immune_checkpoint_blockade" class="mw-redirect" title="Immune checkpoint blockade">immune checkpoint blockade</a>. </p><p>Combination therapy using both anti-PD1 along with anti-<a href="/wiki/CTLA-4" class="mw-redirect" title="CTLA-4">CTLA4</a> therapeutics have emerged as important tumor treatments within the field of <a href="/wiki/Checkpoint_inhibition" class="mw-redirect" title="Checkpoint inhibition">checkpoint inhibition</a>. </p><p>A combination of PD1 and CTLA4 antibodies has been shown to be more effective than either antibody alone in the treatment of a variety of cancers. The effects of the two antibodies do not appear to be redundant.<sup id="cite_ref-:1_7-6" class="reference"><a href="#cite_note-:1-7"><span class="cite-bracket">[</span>7<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-32" class="reference"><a href="#cite_note-32"><span class="cite-bracket">[</span>32<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-33" class="reference"><a href="#cite_note-33"><span class="cite-bracket">[</span>33<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-34" class="reference"><a href="#cite_note-34"><span class="cite-bracket">[</span>34<span class="cite-bracket">]</span></a></sup> Anti-CTLA4 treatment leads to an enhanced antigen specific T cell dependent immune reaction while anti-PD-1 appears to reactivate <a href="/wiki/Cytotoxic_T_cell" title="Cytotoxic T cell">CD8+ T cells</a> ability to lyse cancer cells.<sup id="cite_ref-:1_7-7" class="reference"><a href="#cite_note-:1-7"><span class="cite-bracket">[</span>7<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-ReferenceA_35-0" class="reference"><a href="#cite_note-ReferenceA-35"><span class="cite-bracket">[</span>35<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-36" class="reference"><a href="#cite_note-36"><span class="cite-bracket">[</span>36<span class="cite-bracket">]</span></a></sup> </p><p>In clinical trials, combination therapy has been shown to be effective in reducing tumor size in patients that are unresponsive to single co-inhibitory blockade, despite increasing levels of toxicity due to anti-CTLA4 treatment.<sup id="cite_ref-Chen_DS_2013_37-0" class="reference"><a href="#cite_note-Chen_DS_2013-37"><span class="cite-bracket">[</span>37<span class="cite-bracket">]</span></a></sup> A combination of PD1 and CTLA4 induced up to a ten-fold higher number of CD8+ T cells that are actively infiltrating the tumor tissue.<sup id="cite_ref-ReferenceA_35-1" class="reference"><a href="#cite_note-ReferenceA-35"><span class="cite-bracket">[</span>35<span class="cite-bracket">]</span></a></sup> The authors hypothesized that the higher levels of CD8+ T cell infiltration was due to anti-CTLA-4 inhibited the conversion of CD4 T cells to T regulator cells and further reduced T regulatory suppression with anti-PD-1. This combination promoted a more robust inflammatory response to the tumor that reduced the size of the cancer. Most recently, the FDA has approved a combination therapy with both anti-CTLA4 (<a href="/wiki/Ipilimumab" title="Ipilimumab">ipilimumab</a>) and anti-PD1 (<a href="/wiki/Nivolumab" title="Nivolumab">nivolumab</a>) in October 2015.<sup id="cite_ref-Topalian_2016_38-0" class="reference"><a href="#cite_note-Topalian_2016-38"><span class="cite-bracket">[</span>38<span class="cite-bracket">]</span></a></sup> </p><p>The molecular factors and receptors necessary making a tumor receptive to anti-PD1 treatment remains unknown. <a href="/wiki/PD-L1" title="PD-L1">PD-L1</a> expression on the surface on cancer cells plays a significant role. PD-L1 positive tumors were twice as likely to respond to combination treatment.<sup id="cite_ref-Topalian_2016_38-1" class="reference"><a href="#cite_note-Topalian_2016-38"><span class="cite-bracket">[</span>38<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-Chen_DS_2013_37-1" class="reference"><a href="#cite_note-Chen_DS_2013-37"><span class="cite-bracket">[</span>37<span class="cite-bracket">]</span></a></sup> However patients with PD-L1 negative tumors also have limited response to anti-PD1, demonstrating that PD-L1 expression is not an absolute determinant of the effectiveness of therapy.<sup id="cite_ref-Topalian_2016_38-2" class="reference"><a href="#cite_note-Topalian_2016-38"><span class="cite-bracket">[</span>38<span class="cite-bracket">]</span></a></sup> </p><p>Higher mutational burden in the tumor is correlated with a greater effect of the anti-PD-1 treatment. In clinical trials, patients who benefited from anti-PD1 treatment had cancers, such as melanoma, bladder cancer, and gastric cancer, that had a median higher average number of mutations than the patients who did not respond to the therapy. However, the correlation between higher tumor burden and the clinical effectiveness of PD-1 immune blockade is still uncertain.<sup id="cite_ref-Topalian_2016_38-3" class="reference"><a href="#cite_note-Topalian_2016-38"><span class="cite-bracket">[</span>38<span class="cite-bracket">]</span></a></sup> </p><p>The 2018 <a href="/wiki/Nobel_Prize_for_Medicine" class="mw-redirect" title="Nobel Prize for Medicine">Nobel Prize for Medicine</a> was awarded to <a href="/wiki/James_P._Allison" title="James P. Allison">James P Allison</a> and <a href="/wiki/Tasuku_Honjo" title="Tasuku Honjo">Tasuku Honjo</a> "for their discovery of cancer therapy by inhibition of negative immune regulation". </p> <div class="mw-heading mw-heading3"><h3 id="Anti-PD-1_therapeutics">Anti-PD-1 therapeutics</h3><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Programmed_cell_death_protein_1&action=edit&section=7" title="Edit section: Anti-PD-1 therapeutics"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <style data-mw-deduplicate="TemplateStyles:r1236090951">.mw-parser-output .hatnote{font-style:italic}.mw-parser-output div.hatnote{padding-left:1.6em;margin-bottom:0.5em}.mw-parser-output .hatnote i{font-style:normal}.mw-parser-output .hatnote+link+.hatnote{margin-top:-0.5em}@media print{body.ns-0 .mw-parser-output .hatnote{display:none!important}}</style><div role="note" class="hatnote navigation-not-searchable">Main article: <a href="/wiki/PD-1_and_PD-L1_inhibitors" title="PD-1 and PD-L1 inhibitors">PD-1 and PD-L1 inhibitors</a></div> <p>A number of cancer immunotherapy agents that target the PD-1 receptor have been developed. </p><p>One such anti-PD-1 antibody drug, <a href="/wiki/Nivolumab" title="Nivolumab">nivolumab</a>, (Opdivo - <a href="/wiki/Bristol_Myers_Squibb" title="Bristol Myers Squibb">Bristol Myers Squibb</a>), produced complete or partial responses in non-small-cell lung cancer, melanoma, and renal-cell cancer, in a clinical trial with a total of 296 patients.<sup id="cite_ref-Topalian_2012_39-0" class="reference"><a href="#cite_note-Topalian_2012-39"><span class="cite-bracket">[</span>39<span class="cite-bracket">]</span></a></sup> Colon and pancreatic cancer did not have a response. <a href="/wiki/Nivolumab" title="Nivolumab">Nivolumab</a> (Opdivo, Bristol-Myers Squibb) was approved in Japan in July 2014 and by the US FDA in December 2014 to treat metastatic <a href="/wiki/Melanoma" title="Melanoma">melanoma</a>. </p><p><a href="/wiki/Pembrolizumab" title="Pembrolizumab">Pembrolizumab</a> (Keytruda, MK-3475, Merck), which also targets PD-1 receptors, was approved by the FDA in Sept 2014 to treat metastatic <a href="/wiki/Melanoma" title="Melanoma">melanoma</a>. Pembrolizumab has been made accessible to advanced melanoma patients in the UK via UK Early Access to Medicines Scheme (EAMS) in March 2015. It is being used in clinical trials in the US for lung cancer, lymphoma, and mesothelioma. It has had measured success, with little side effects.<sup id="cite_ref-:1_7-8" class="reference"><a href="#cite_note-:1-7"><span class="cite-bracket">[</span>7<span class="cite-bracket">]</span></a></sup> It is up to the manufacturer of the drug to submit application to the FDA for approval for use in these diseases. On October 2, 2015, Pembrolizumab was approved by FDA for advanced (metastatic) non-small cell lung cancer (NSCLC) patients whose disease has progressed after other treatments.<sup id="cite_ref-40" class="reference"><a href="#cite_note-40"><span class="cite-bracket">[</span>40<span class="cite-bracket">]</span></a></sup> </p><p><a href="/wiki/Toripalimab" title="Toripalimab">Toripalimab</a> is a humanized IgG4 monoclonal antibody against PD-1 which was approved in China in 2018 and in the United States in 2023.<sup id="cite_ref-41" class="reference"><a href="#cite_note-41"><span class="cite-bracket">[</span>41<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-Keam_42-0" class="reference"><a href="#cite_note-Keam-42"><span class="cite-bracket">[</span>42<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-43" class="reference"><a href="#cite_note-43"><span class="cite-bracket">[</span>43<span class="cite-bracket">]</span></a></sup> </p><p>Drugs in early stage development targeting PD-1 receptors (<a href="/wiki/Checkpoint_inhibitor" title="Checkpoint inhibitor">checkpoint inhibitors</a>) include <a href="/wiki/Pidilizumab" title="Pidilizumab">pidilizumab</a> (CT-011, Cure Tech) and <a href="/w/index.php?title=BMS-936559&action=edit&redlink=1" class="new" title="BMS-936559 (page does not exist)">BMS-936559</a> (Bristol Myers Squibb). Both <a href="/wiki/Atezolizumab" title="Atezolizumab">atezolizumab</a> (MPDL3280A, Roche) and <a href="/wiki/Avelumab" title="Avelumab">avelumab</a> (<a href="/wiki/Merck_KGaA" class="mw-redirect" title="Merck KGaA">Merck KGaA, Darmstadt, Germany</a> and <a href="/wiki/Pfizer" title="Pfizer">Pfizer</a>) target the similar PD-L1 receptor. </p> <div class="mw-heading mw-heading2"><h2 id="Animal_studies">Animal studies</h2><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Programmed_cell_death_protein_1&action=edit&section=8" title="Edit section: Animal studies"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <div class="mw-heading mw-heading3"><h3 id="HIV">HIV</h3><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Programmed_cell_death_protein_1&action=edit&section=9" title="Edit section: HIV"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <p>Drugs targeting PD-1 in combination with other negative immune checkpoint receptors, such as (<a href="/wiki/TIGIT" title="TIGIT">TIGIT</a>), may augment immune responses and/or facilitate <a href="/wiki/HIV" title="HIV">HIV</a> eradication.<sup id="cite_ref-pmid22198819_44-0" class="reference"><a href="#cite_note-pmid22198819-44"><span class="cite-bracket">[</span>44<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-Marks_Exhausted_45-0" class="reference"><a href="#cite_note-Marks_Exhausted-45"><span class="cite-bracket">[</span>45<span class="cite-bracket">]</span></a></sup> T lymphocytes exhibit elevated expression of PD-1 in cases of chronic HIV infection.<sup id="cite_ref-Velu_14_46-0" class="reference"><a href="#cite_note-Velu_14-46"><span class="cite-bracket">[</span>46<span class="cite-bracket">]</span></a></sup> Heightened presence of the PD-1 receptors corresponds to exhaustion of the HIV specific CD8+ cytotoxic and CD4+ helper T cell populations that are vital in combating the virus. Immune blockade of PD-1 resulted in restoration of T cell inflammatory phenotype necessary to combat the progression of disease.<sup id="cite_ref-Velu_14_46-1" class="reference"><a href="#cite_note-Velu_14-46"><span class="cite-bracket">[</span>46<span class="cite-bracket">]</span></a></sup> </p> <div class="mw-heading mw-heading3"><h3 id="Alzheimer's_disease"><span id="Alzheimer.27s_disease"></span>Alzheimer's disease</h3><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Programmed_cell_death_protein_1&action=edit&section=10" title="Edit section: Alzheimer's disease"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <p>Blocking of PD-1 leads to a reduction in cerebral amyloid-β plaques and improves cognitive performance in mice.<sup id="cite_ref-Baruch_135–137_47-0" class="reference"><a href="#cite_note-Baruch_135–137-47"><span class="cite-bracket">[</span>47<span class="cite-bracket">]</span></a></sup> Immune blockade of PD-1 evoked an IFN-γ dependent immune response that recruited monocyte-derived macrophages to the brain that were then capable of clearing the amyloid-β plaques from the tissue. Repeated administrations with anti-PD-1 were found to be necessary to maintain the therapeutic effects of the treatment. Amyloid fibrils are immunosuppressive and this finding has been separately confirmed by examining the effects of the fibrils in neuroinflammatory diseases.<sup id="cite_ref-48" class="reference"><a href="#cite_note-48"><span class="cite-bracket">[</span>48<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-49" class="reference"><a href="#cite_note-49"><span class="cite-bracket">[</span>49<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-50" class="reference"><a href="#cite_note-50"><span class="cite-bracket">[</span>50<span class="cite-bracket">]</span></a></sup> PD-1 counteracts the effects of the fibrils by boosting immune activity and triggering an immune pathway that allows for brain repair.<sup id="cite_ref-Baruch_135–137_47-1" class="reference"><a href="#cite_note-Baruch_135–137-47"><span class="cite-bracket">[</span>47<span class="cite-bracket">]</span></a></sup> </p> <div class="mw-heading mw-heading2"><h2 id="References">References</h2><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Programmed_cell_death_protein_1&action=edit&section=11" title="Edit section: References"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <style data-mw-deduplicate="TemplateStyles:r1239543626">.mw-parser-output .reflist{margin-bottom:0.5em;list-style-type:decimal}@media screen{.mw-parser-output .reflist{font-size:90%}}.mw-parser-output .reflist .references{font-size:100%;margin-bottom:0;list-style-type:inherit}.mw-parser-output .reflist-columns-2{column-width:30em}.mw-parser-output .reflist-columns-3{column-width:25em}.mw-parser-output .reflist-columns{margin-top:0.3em}.mw-parser-output .reflist-columns ol{margin-top:0}.mw-parser-output .reflist-columns li{page-break-inside:avoid;break-inside:avoid-column}.mw-parser-output .reflist-upper-alpha{list-style-type:upper-alpha}.mw-parser-output .reflist-upper-roman{list-style-type:upper-roman}.mw-parser-output .reflist-lower-alpha{list-style-type:lower-alpha}.mw-parser-output .reflist-lower-greek{list-style-type:lower-greek}.mw-parser-output .reflist-lower-roman{list-style-type:lower-roman}</style><div class="reflist reflist-columns references-column-width" style="column-width: 33em;"> <ol class="references"> <li id="cite_note-refGRCh38Ensembl-1"><span class="mw-cite-backlink">^ <a href="#cite_ref-refGRCh38Ensembl_1-0"><sup><i><b>a</b></i></sup></a> <a href="#cite_ref-refGRCh38Ensembl_1-1"><sup><i><b>b</b></i></sup></a> <a href="#cite_ref-refGRCh38Ensembl_1-2"><sup><i><b>c</b></i></sup></a></span> <span class="reference-text"><a rel="nofollow" class="external text" href="http://May2017.archive.ensembl.org/Homo_sapiens/Gene/Summary?db=core;g=ENSG00000188389,">ENSG00000276977 GRCh38: Ensembl release 89: ENSG00000188389, ENSG00000276977</a> – <a href="/wiki/Ensembl_genome_database_project" title="Ensembl genome database project">Ensembl</a>, May 2017</span> </li> <li 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class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Programmed_cell_death_protein_1&action=edit&section=12" title="Edit section: Further reading"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <style data-mw-deduplicate="TemplateStyles:r1239549316">.mw-parser-output .refbegin{margin-bottom:0.5em}.mw-parser-output .refbegin-hanging-indents>ul{margin-left:0}.mw-parser-output .refbegin-hanging-indents>ul>li{margin-left:0;padding-left:3.2em;text-indent:-3.2em}.mw-parser-output .refbegin-hanging-indents ul,.mw-parser-output .refbegin-hanging-indents ul li{list-style:none}@media(max-width:720px){.mw-parser-output .refbegin-hanging-indents>ul>li{padding-left:1.6em;text-indent:-1.6em}}.mw-parser-output .refbegin-columns{margin-top:0.3em}.mw-parser-output .refbegin-columns ul{margin-top:0}.mw-parser-output .refbegin-columns li{page-break-inside:avoid;break-inside:avoid-column}@media screen{.mw-parser-output .refbegin{font-size:90%}}</style><div class="refbegin refbegin-columns references-column-width" style="column-width: 33em"> <ul><li><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1238218222" /><cite id="CITEREFVibhakarJuanTraganosDarzynkiewicz1997" class="citation journal cs1">Vibhakar R, Juan G, Traganos F, Darzynkiewicz Z, Finger LR (April 1997). 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title="ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.jtitle=The+Journal+of+Rheumatology&rft.atitle=Enhanced+expression+of+programmed+death-1+%28PD-1%29%2FPD-L1+in+salivary+glands+of+patients+with+Sj%C3%B6gren%27s+syndrome&rft.volume=32&rft.issue=11&rft.pages=%3Cspan+class%3D%22nowrap%22%3E2156-%3C%2Fspan%3E63&rft.date=2005-11&rft_id=info%3Apmid%2F16265694&rft.aulast=Kobayashi&rft.aufirst=M&rft.au=Kawano%2C+S&rft.au=Hatachi%2C+S&rft.au=Kurimoto%2C+C&rft.au=Okazaki%2C+T&rft.au=Iwai%2C+Y&rft.au=Honjo%2C+T&rft.au=Tanaka%2C+Y&rft.au=Minato%2C+N&rft.au=Komori%2C+T&rft.au=Maeda%2C+S&rft.au=Kumagai%2C+S&rfr_id=info%3Asid%2Fen.wikipedia.org%3AProgrammed+cell+death+protein+1" class="Z3988"></span></li></ul> </div> <div class="mw-heading mw-heading2"><h2 id="External_links">External links</h2><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Programmed_cell_death_protein_1&action=edit&section=13" title="Edit section: External links"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <ul><li><a rel="nofollow" class="external text" href="https://meshb.nlm.nih.gov/record/ui?name=PDCD1+protein%2C+human">PDCD1+protein,+human</a> at the U.S. National Library of Medicine <a href="/wiki/Medical_Subject_Headings" title="Medical Subject Headings">Medical Subject Headings</a> (MeSH)</li> <li>Overview of all the structural information available in the <a href="/wiki/Protein_Data_Bank" title="Protein Data Bank">PDB</a> for <a href="/wiki/UniProt" title="UniProt">UniProt</a>: <i><a rel="nofollow" class="external text" href="https://www.ebi.ac.uk/pdbe/pdbe-kb/proteins/Q15116">Q15116</a></i> (Programmed cell death protein 1) at the <a href="/wiki/PDBe-KB" title="PDBe-KB">PDBe-KB</a>.</li></ul> <p><i>This article incorporates text from the <a href="/wiki/United_States_National_Library_of_Medicine" title="United States National Library of Medicine">United States National Library of Medicine</a>, which is in the <a href="/wiki/Public_domain" title="Public domain">public domain</a>.</i> </p> <div class="navbox-styles"><style data-mw-deduplicate="TemplateStyles:r1129693374">.mw-parser-output .hlist dl,.mw-parser-output .hlist ol,.mw-parser-output .hlist ul{margin:0;padding:0}.mw-parser-output .hlist dd,.mw-parser-output .hlist dt,.mw-parser-output .hlist li{margin:0;display:inline}.mw-parser-output .hlist.inline,.mw-parser-output .hlist.inline dl,.mw-parser-output .hlist.inline ol,.mw-parser-output .hlist.inline ul,.mw-parser-output .hlist dl dl,.mw-parser-output .hlist dl ol,.mw-parser-output .hlist dl ul,.mw-parser-output .hlist ol dl,.mw-parser-output .hlist ol ol,.mw-parser-output .hlist ol ul,.mw-parser-output .hlist ul dl,.mw-parser-output .hlist ul ol,.mw-parser-output .hlist ul ul{display:inline}.mw-parser-output .hlist .mw-empty-li{display:none}.mw-parser-output .hlist dt::after{content:": "}.mw-parser-output .hlist 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.navbox-abovebelow{background-color:#e6e6ff}.mw-parser-output .navbox-even{background-color:#f7f7f7}.mw-parser-output .navbox-odd{background-color:transparent}.mw-parser-output .navbox .hlist td dl,.mw-parser-output .navbox .hlist td ol,.mw-parser-output .navbox .hlist td ul,.mw-parser-output .navbox td.hlist dl,.mw-parser-output .navbox td.hlist ol,.mw-parser-output .navbox td.hlist ul{padding:0.125em 0}.mw-parser-output .navbox .navbar{display:block;font-size:100%}.mw-parser-output .navbox-title .navbar{float:left;text-align:left;margin-right:0.5em}body.skin--responsive .mw-parser-output .navbox-image img{max-width:none!important}@media print{body.ns-0 .mw-parser-output .navbox{display:none!important}}</style></div><div role="navigation" class="navbox" aria-labelledby="Proteins:_clusters_of_differentiation_(see_also_list_of_human_clusters_of_differentiation)188" style="padding:3px"><table class="nowraplinks mw-collapsible mw-collapsed navbox-inner" style="border-spacing:0;background:transparent;color:inherit"><tbody><tr><th scope="col" class="navbox-title" colspan="2" style="background:#e7dcc3"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1129693374" /><style data-mw-deduplicate="TemplateStyles:r1239400231">.mw-parser-output .navbar{display:inline;font-size:88%;font-weight:normal}.mw-parser-output .navbar-collapse{float:left;text-align:left}.mw-parser-output .navbar-boxtext{word-spacing:0}.mw-parser-output .navbar ul{display:inline-block;white-space:nowrap;line-height:inherit}.mw-parser-output .navbar-brackets::before{margin-right:-0.125em;content:"[ "}.mw-parser-output .navbar-brackets::after{margin-left:-0.125em;content:" ]"}.mw-parser-output .navbar li{word-spacing:-0.125em}.mw-parser-output .navbar a>span,.mw-parser-output .navbar a>abbr{text-decoration:inherit}.mw-parser-output .navbar-mini abbr{font-variant:small-caps;border-bottom:none;text-decoration:none;cursor:inherit}.mw-parser-output .navbar-ct-full{font-size:114%;margin:0 7em}.mw-parser-output .navbar-ct-mini{font-size:114%;margin:0 4em}html.skin-theme-clientpref-night .mw-parser-output .navbar li a abbr{color:var(--color-base)!important}@media(prefers-color-scheme:dark){html.skin-theme-clientpref-os .mw-parser-output .navbar li a abbr{color:var(--color-base)!important}}@media print{.mw-parser-output .navbar{display:none!important}}</style><div class="navbar plainlinks hlist navbar-mini"><ul><li class="nv-view"><a href="/wiki/Template:Clusters_of_differentiation" title="Template:Clusters of differentiation"><abbr title="View this template">v</abbr></a></li><li class="nv-talk"><a href="/wiki/Template_talk:Clusters_of_differentiation" title="Template talk:Clusters of differentiation"><abbr title="Discuss this template">t</abbr></a></li><li class="nv-edit"><a href="/wiki/Special:EditPage/Template:Clusters_of_differentiation" title="Special:EditPage/Template:Clusters of differentiation"><abbr title="Edit this template">e</abbr></a></li></ul></div><div id="Proteins:_clusters_of_differentiation_(see_also_list_of_human_clusters_of_differentiation)188" style="font-size:114%;margin:0 4em"><a href="/wiki/Protein" title="Protein">Proteins</a>: <a href="/wiki/Cluster_of_differentiation" title="Cluster of differentiation">clusters of differentiation</a> (see also <a href="/wiki/List_of_human_clusters_of_differentiation" title="List of human clusters of differentiation">list of human clusters of differentiation</a>)</div></th></tr><tr><th scope="row" class="navbox-group" style="width:1%;background-color: AntiqueWhite">1–50</th><td class="navbox-list-with-group navbox-list navbox-odd hlist" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><a href="/wiki/CD1" title="CD1">CD1</a> <ul><li><a href="/wiki/Group_1_CD1" class="mw-redirect" title="Group 1 CD1">a-c</a></li> <li><a href="/wiki/CD1A" title="CD1A">1A</a></li> <li><a href="/wiki/CD1b" title="CD1b">1B</a></li> <li><a href="/wiki/CD1D" title="CD1D">1D</a></li> <li><a href="/wiki/CD1E" title="CD1E">1E</a></li></ul></li> <li><a href="/wiki/CD2" title="CD2">CD2</a></li> <li><a href="/wiki/CD3_(immunology)" title="CD3 (immunology)">CD3</a> <ul><li><a href="/wiki/CD3G" title="CD3G">γ</a></li> <li><a href="/wiki/CD3D" title="CD3D">δ</a></li> <li><a href="/wiki/CD3E" class="mw-redirect" title="CD3E">ε</a></li></ul></li> <li><a href="/wiki/CD4" title="CD4">CD4</a></li> <li><a href="/wiki/CD5_(protein)" title="CD5 (protein)">CD5</a></li> <li><a href="/wiki/CD6" title="CD6">CD6</a></li> <li><a href="/wiki/CD7" title="CD7">CD7</a></li> <li><a href="/wiki/CD8" title="CD8">CD8</a> <ul><li><a href="/wiki/CD8A" title="CD8A">a</a></li></ul></li> <li><a href="/wiki/CD9" title="CD9">CD9</a></li> <li><a href="/wiki/Neprilysin" title="Neprilysin">CD10</a></li> <li><i>CD11</i> <ul><li><a href="/wiki/CD11a" class="mw-redirect" title="CD11a">a</a></li> <li><a href="/wiki/Integrin_alpha_M" title="Integrin alpha M">b</a></li> <li><a href="/wiki/CD11c" class="mw-redirect" title="CD11c">c</a></li> <li><a href="/wiki/ITGAD" class="mw-redirect" title="ITGAD">d</a></li></ul></li> <li><a href="/wiki/Alanine_aminopeptidase" title="Alanine aminopeptidase">CD13</a></li> <li><a href="/wiki/CD14" title="CD14">CD14</a></li> <li><a href="/wiki/CD15" class="mw-redirect" title="CD15">CD15</a></li> <li><a href="/wiki/CD16" title="CD16">CD16</a> <ul><li><a href="/wiki/FCGR3A" title="FCGR3A">A</a></li> <li><a href="/wiki/FCGR3B" title="FCGR3B">B</a></li></ul></li> <li><a href="/wiki/CD18" class="mw-redirect" title="CD18">CD18</a></li> <li><a href="/wiki/CD19" title="CD19">CD19</a></li> <li><a href="/wiki/CD20" title="CD20">CD20</a></li> <li><a href="/wiki/Complement_receptor_2" title="Complement receptor 2">CD21</a></li> <li><a href="/wiki/CD22" title="CD22">CD22</a></li> <li><a href="/wiki/CD23" title="CD23">CD23</a></li> <li><a href="/wiki/CD24" title="CD24">CD24</a></li> <li><a href="/wiki/IL2RA" title="IL2RA">CD25</a></li> <li><a href="/wiki/Dipeptidyl_peptidase-4" title="Dipeptidyl peptidase-4">CD26</a></li> <li><a href="/wiki/CD27" title="CD27">CD27</a></li> <li><a href="/wiki/CD28" title="CD28">CD28</a></li> <li><a href="/wiki/Integrin_beta_1" title="Integrin beta 1">CD29</a></li> <li><a href="/wiki/CD30" title="CD30">CD30</a></li> <li><a href="/wiki/CD31" title="CD31">CD31</a></li> <li><a href="/wiki/CD32" title="CD32">CD32</a> <ul><li><a href="/wiki/FCGR2A" title="FCGR2A">A</a></li> <li><a href="/wiki/FCGR2B" title="FCGR2B">B</a></li></ul></li> <li><a href="/wiki/CD33" title="CD33">CD33</a></li> <li><a href="/wiki/CD34" title="CD34">CD34</a></li> <li><a href="/wiki/Complement_receptor_1" title="Complement receptor 1">CD35</a></li> <li><a href="/wiki/CD36" title="CD36">CD36</a></li> <li><a href="/wiki/CD37" title="CD37">CD37</a></li> <li><a href="/wiki/CD38" title="CD38">CD38</a></li> <li><a href="/wiki/ENTPD1" title="ENTPD1">CD39</a></li> <li><a href="/wiki/CD40_(protein)" title="CD40 (protein)">CD40</a></li> <li><a href="/wiki/ITGA2B" class="mw-redirect" title="ITGA2B">CD41</a></li> <li><a href="/wiki/Glycoprotein_Ib" title="Glycoprotein Ib">CD42</a> <ul><li><a href="/wiki/Glycoprotein_IX" title="Glycoprotein IX">a</a></li> <li><a href="/wiki/GP1BA" title="GP1BA">b</a></li> <li><a href="/wiki/GP1BB" title="GP1BB">c</a></li> <li><a href="/wiki/GP5_(gene)" title="GP5 (gene)">d</a></li></ul></li> <li><a href="/wiki/CD43" title="CD43">CD43</a></li> <li><a href="/wiki/CD44" title="CD44">CD44</a></li> <li><a href="/wiki/PTPRC" title="PTPRC">CD45</a></li> <li><a href="/wiki/CD46" title="CD46">CD46</a></li> <li><a href="/wiki/CD47" title="CD47">CD47</a></li> <li><a href="/wiki/CD48" title="CD48">CD48</a></li> <li><i>CD49</i> <ul><li><a href="/wiki/CD49a" class="mw-redirect" title="CD49a">a</a></li> <li><a href="/wiki/CD49b" class="mw-redirect" title="CD49b">b</a></li> <li><a href="/wiki/CD49c" class="mw-redirect" title="CD49c">c</a></li> <li><a href="/wiki/CD49d" class="mw-redirect" title="CD49d">d</a></li> <li><a href="/wiki/ITGA5" class="mw-redirect" title="ITGA5">e</a></li> <li><a href="/wiki/ITGA6" class="mw-redirect" title="ITGA6">f</a></li></ul></li> <li><a href="/wiki/ICAM3" title="ICAM3">CD50</a></li></ul> </div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%;background-color: AntiqueWhite">51–100</th><td class="navbox-list-with-group navbox-list navbox-even hlist" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><a href="/wiki/ITGAV" class="mw-redirect" title="ITGAV">CD51</a></li> <li><a href="/wiki/CD52" title="CD52">CD52</a></li> <li><a href="/wiki/CD53" title="CD53">CD53</a></li> <li><a href="/wiki/ICAM-1" title="ICAM-1">CD54</a></li> <li><a href="/wiki/Decay-accelerating_factor" title="Decay-accelerating factor">CD55</a></li> <li><a href="/wiki/Neural_cell_adhesion_molecule" title="Neural cell adhesion molecule">CD56</a></li> <li><a href="/wiki/B3GAT1" title="B3GAT1">CD57</a></li> <li><a href="/wiki/CD58" title="CD58">CD58</a></li> <li><a href="/wiki/CD59" title="CD59">CD59</a></li> <li><a href="/wiki/CD61" class="mw-redirect" title="CD61">CD61</a></li> <li><a href="/wiki/Selectin" title="Selectin">CD62</a> <ul><li><a href="/wiki/E-selectin" title="E-selectin">E</a></li> <li><a href="/wiki/L-selectin" title="L-selectin">L</a></li> <li><a href="/wiki/P-selectin" title="P-selectin">P</a></li></ul></li> <li><a href="/wiki/CD63" title="CD63">CD63</a></li> <li><a href="/wiki/CD64_(biology)" title="CD64 (biology)">CD64</a> <ul><li><a href="/wiki/FCGR1A" title="FCGR1A">A</a></li> <li><a href="/wiki/FCGR1B" class="mw-redirect" title="FCGR1B">B</a></li> <li><a href="/wiki/FCGR1C" class="mw-redirect" title="FCGR1C">C</a></li></ul></li> <li><a href="/wiki/Carcinoembryonic_antigen" title="Carcinoembryonic antigen">CD66</a> <ul><li><a href="/wiki/CEACAM1" title="CEACAM1">a</a></li> <li><a href="/wiki/CEACAM8" title="CEACAM8">b</a></li> <li><a href="/wiki/CEACAM6" title="CEACAM6">c</a></li> <li><a href="/wiki/CEACAM3" title="CEACAM3">d</a></li> <li><a href="/wiki/CEACAM5" title="CEACAM5">e</a></li> <li><a href="/wiki/PSG1_(gene)" class="mw-redirect" title="PSG1 (gene)">f</a></li></ul></li> <li><a href="/wiki/CD68" title="CD68">CD68</a></li> <li><a href="/wiki/CD69" title="CD69">CD69</a></li> <li><a href="/wiki/CD70" title="CD70">CD70</a></li> <li><a href="/wiki/TFRC" class="mw-redirect" title="TFRC">CD71</a></li> <li><a href="/wiki/CD72" title="CD72">CD72</a></li> <li><a href="/wiki/NT5E" title="NT5E">CD73</a></li> <li><a href="/wiki/CD74" title="CD74">CD74</a></li> <li><a href="/wiki/CD78" title="CD78">CD78</a></li> <li><a href="/wiki/CD79" title="CD79">CD79</a> <ul><li><a href="/wiki/CD79A" title="CD79A">a</a></li> <li><a href="/wiki/CD79B" title="CD79B">b</a></li></ul></li> <li><a href="/wiki/CD80" title="CD80">CD80</a></li> <li><a href="/wiki/CD81" title="CD81">CD81</a></li> <li><a href="/wiki/CD82_(gene)" title="CD82 (gene)">CD82</a></li> <li><a href="/wiki/CD83" title="CD83">CD83</a></li> <li><a href="/wiki/CD84" title="CD84">CD84</a></li> <li><i>CD85</i> <ul><li><a href="/wiki/LILRB3" title="LILRB3">a</a></li> <li><a href="/wiki/LILRB2" title="LILRB2">d</a></li> <li><a href="/wiki/LILRA3" title="LILRA3">e</a></li> <li><a href="/wiki/LILRA2" title="LILRA2">h</a></li> <li><a href="/wiki/LILRB1" title="LILRB1">j</a></li> <li><a href="/wiki/LILRB4" title="LILRB4">k</a></li></ul></li> <li><a href="/wiki/CD86" title="CD86">CD86</a></li> <li><a href="/wiki/Urokinase_receptor" title="Urokinase receptor">CD87</a></li> <li><a href="/wiki/C5a_receptor" title="C5a receptor">CD88</a></li> <li><a href="/wiki/FCAR" title="FCAR">CD89</a></li> <li><a href="/wiki/CD90" title="CD90">CD90</a></li> <li><a href="/wiki/LRP1" title="LRP1">CD91</a> - <a href="/wiki/SLC44A1" class="mw-redirect" title="SLC44A1">CD92</a></li> <li><a href="/wiki/CD93" title="CD93">CD93</a></li> <li><a href="/wiki/KLRD1" title="KLRD1">CD94</a></li> <li><a href="/wiki/Fas_receptor" title="Fas receptor">CD95</a></li> <li><a href="/wiki/CD96" title="CD96">CD96</a></li> <li><a href="/wiki/CD97" title="CD97">CD97</a></li> <li><a href="/wiki/CD98" title="CD98">CD98</a></li> <li><a href="/wiki/CD99" title="CD99">CD99</a></li> <li><a href="/wiki/SEMA4D" title="SEMA4D">CD100</a></li></ul> </div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%;background-color: AntiqueWhite">101–150</th><td class="navbox-list-with-group navbox-list navbox-odd hlist" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><a href="/wiki/IGSF2" title="IGSF2">CD101</a></li> <li><a href="/wiki/ICAM2" title="ICAM2">CD102</a></li> <li><a href="/wiki/ITGAE" title="ITGAE">CD103</a></li> <li><a href="/wiki/ITGB4" class="mw-redirect" title="ITGB4">CD104</a></li> <li><a href="/wiki/Endoglin" title="Endoglin">CD105</a></li> <li><a href="/wiki/VCAM-1" title="VCAM-1">CD106</a></li> <li><i>CD107</i> <ul><li><a href="/wiki/LAMP1" title="LAMP1">a</a></li> <li><a href="/wiki/LAMP2" title="LAMP2">b</a></li></ul></li> <li><a href="/wiki/SEMA7A" title="SEMA7A">CD108</a></li> <li><a href="/wiki/CD109" title="CD109">CD109</a></li> <li><a href="/wiki/Myeloproliferative_leukemia_virus_oncogene" class="mw-redirect" title="Myeloproliferative leukemia virus oncogene">CD110</a></li> <li><a href="/wiki/PVRL1" class="mw-redirect" title="PVRL1">CD111</a></li> <li><a href="/wiki/PVRL2" class="mw-redirect" title="PVRL2">CD112</a></li> <li><a href="/wiki/PVRL3" class="mw-redirect" title="PVRL3">CD113</a></li> <li><a href="/wiki/Granulocyte_colony-stimulating_factor_receptor" title="Granulocyte colony-stimulating factor receptor">CD114</a></li> <li><a href="/wiki/Colony_stimulating_factor_1_receptor" title="Colony stimulating factor 1 receptor">CD115</a></li> <li><a href="/wiki/Granulocyte_macrophage_colony-stimulating_factor_receptor" class="mw-redirect" title="Granulocyte macrophage colony-stimulating factor receptor">CD116</a></li> <li><a href="/wiki/KIT_(gene)" title="KIT (gene)">CD117</a></li> <li><a href="/wiki/Leukemia_inhibitory_factor_receptor" title="Leukemia inhibitory factor receptor">CD118</a></li> <li><a href="/wiki/Interferon_gamma_receptor_1" title="Interferon gamma receptor 1">CD119</a></li> <li><a href="/wiki/CD120" title="CD120">CD120</a> <ul><li><a href="/wiki/TNFRSF1A" class="mw-redirect" title="TNFRSF1A">a</a></li> <li><a href="/wiki/TNFRSF1B" class="mw-redirect" title="TNFRSF1B">b</a></li></ul></li> <li><i>CD121</i> <ul><li><a href="/wiki/Interleukin_1_receptor,_type_I" title="Interleukin 1 receptor, type I">a</a></li> <li><a href="/wiki/Interleukin_1_receptor,_type_II" title="Interleukin 1 receptor, type II">b</a></li></ul></li> <li><a href="/wiki/IL2RB" title="IL2RB">CD122</a></li> <li><a href="/wiki/IL3RA" title="IL3RA">CD123</a></li> <li><a href="/wiki/Interleukin-4_receptor" title="Interleukin-4 receptor">CD124</a></li> <li><a href="/wiki/Interleukin_5_receptor_alpha_subunit" title="Interleukin 5 receptor alpha subunit">CD125</a></li> <li><a href="/wiki/Interleukin-6_receptor" title="Interleukin-6 receptor">CD126</a></li> <li><a href="/wiki/Interleukin-7_receptor" title="Interleukin-7 receptor">CD127</a></li> <li><a href="/wiki/Interleukin-9_receptor" title="Interleukin-9 receptor">CD129</a></li> <li><a href="/wiki/Glycoprotein_130" title="Glycoprotein 130">CD130</a></li> <li><a href="/wiki/CSF2RB" title="CSF2RB">CD131</a></li> <li><a href="/wiki/Common_gamma_chain" title="Common gamma chain">CD132</a></li> <li><a href="/wiki/CD133" title="CD133">CD133</a></li> <li><a href="/wiki/CD134" title="CD134">CD134</a></li> <li><a href="/wiki/CD135" title="CD135">CD135</a></li> <li><a href="/wiki/MST1R" title="MST1R">CD136</a></li> <li><a href="/wiki/CD137" title="CD137">CD137</a></li> <li><a href="/wiki/Syndecan_1" title="Syndecan 1">CD138</a></li> <li><a href="/wiki/PDGFRB" title="PDGFRB">CD140b</a></li> <li><a href="/wiki/Thrombomodulin" title="Thrombomodulin">CD141</a></li> <li><a href="/wiki/Tissue_factor" title="Tissue factor">CD142</a></li> <li><a href="/wiki/Angiotensin-converting_enzyme" title="Angiotensin-converting enzyme">CD143</a></li> <li><a href="/wiki/VE-cadherin" title="VE-cadherin">CD144</a></li> <li><a href="/wiki/CD146" title="CD146">CD146</a></li> <li><a href="/wiki/Basigin" title="Basigin">CD147</a></li> <li><a href="/wiki/PTPRJ" title="PTPRJ">CD148</a></li> <li><a href="/wiki/SLAMF1" title="SLAMF1">CD150</a></li></ul> </div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%;background-color: AntiqueWhite">151–200</th><td class="navbox-list-with-group navbox-list navbox-even hlist" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><a href="/wiki/CD151" title="CD151">CD151</a></li> <li><a href="/wiki/CTLA-4" class="mw-redirect" title="CTLA-4">CD152</a></li> <li><a href="/wiki/CD153" title="CD153">CD153</a></li> <li><a href="/wiki/CD154" title="CD154">CD154</a></li> <li><a href="/wiki/CD155" title="CD155">CD155</a></li> <li><i>CD156</i> <ul><li><a href="/wiki/ADAM8" title="ADAM8">a</a></li> <li><a href="/wiki/ADAM17" title="ADAM17">b</a></li> <li><a href="/wiki/ADAM10" title="ADAM10">c</a></li></ul></li> <li><a href="/wiki/BST1" title="BST1">CD157</a></li> <li><i>CD158</i> (<a href="/wiki/KIR2DL1" title="KIR2DL1">a</a></li> <li><a href="/wiki/KIR2DL4" title="KIR2DL4">d</a></li> <li><a href="/wiki/KIR3DL1" title="KIR3DL1">e</a></li> <li><a href="/wiki/KIR2DS4" title="KIR2DS4">i</a></li> <li><a href="/wiki/KIR3DL2" title="KIR3DL2">k</a>)</li> <li><i>CD159</i> <ul><li><a href="/wiki/NKG2" title="NKG2">a</a></li> <li><a href="/wiki/KLRC2" title="KLRC2">c</a></li></ul></li> <li><a href="/wiki/CD160" title="CD160">CD160</a></li> <li><a href="/wiki/KLRB1" title="KLRB1">CD161</a></li> <li><a href="/wiki/P-selectin_glycoprotein_ligand-1" title="P-selectin glycoprotein ligand-1">CD162</a></li> <li><a href="/wiki/CD163" title="CD163">CD163</a></li> <li><a href="/wiki/CD164" title="CD164">CD164</a></li> <li><a href="/wiki/ALCAM" title="ALCAM">CD166</a></li> <li><i>CD167</i> <ul><li><a href="/wiki/DDR1" title="DDR1">a</a></li> <li><a href="/wiki/Discoidin_domain-containing_receptor_2" title="Discoidin domain-containing receptor 2">b</a></li></ul></li> <li><a href="/wiki/Hyaluronan-mediated_motility_receptor" title="Hyaluronan-mediated motility receptor">CD168</a></li> <li><a href="/wiki/Sialoadhesin" title="Sialoadhesin">CD169</a></li> <li><a href="/wiki/SIGLEC5" title="SIGLEC5">CD170</a></li> <li><a href="/wiki/L1_(protein)" title="L1 (protein)">CD171</a></li> <li><i>CD172</i> <ul><li><a href="/wiki/Signal-regulatory_protein_alpha" title="Signal-regulatory protein alpha">a</a></li> <li><a href="/wiki/SIRPB1" title="SIRPB1">b</a></li> <li><a href="/wiki/SIRPG" title="SIRPG">g</a></li></ul></li> <li><a href="/wiki/Fucosyltransferase_3" title="Fucosyltransferase 3">CD174</a></li> <li><a href="/wiki/CD177" title="CD177">CD177</a></li> <li><a href="/wiki/Fas_ligand" title="Fas ligand">CD178</a></li> <li><i>CD179</i> <ul><li><a href="/wiki/VPREB1" title="VPREB1">a</a></li> <li><a href="/wiki/IGLL1" title="IGLL1">b</a></li></ul></li> <li><a href="/wiki/CD180" title="CD180">CD180</a></li> <li><a href="/wiki/Interleukin_8_receptor,_alpha" title="Interleukin 8 receptor, alpha">CD181</a></li> <li><a href="/wiki/Interleukin_8_receptor,_beta" title="Interleukin 8 receptor, beta">CD182</a></li> <li><a href="/wiki/CXCR3" title="CXCR3">CD183</a></li> <li><a href="/wiki/CXCR4" title="CXCR4">CD184</a></li> <li><a href="/wiki/CXCR5" title="CXCR5">CD185</a></li> <li><a href="/wiki/CXCR6" title="CXCR6">CD186</a></li> <li><a href="/wiki/CCR1" title="CCR1">CD191</a></li> <li><a href="/wiki/CCR2" title="CCR2">CD192</a></li> <li><a href="/wiki/CCR3_(gene)" title="CCR3 (gene)">CD193</a></li> <li><a href="/wiki/CCR4" title="CCR4">CD194</a></li> <li><a href="/wiki/CCR5" title="CCR5">CD195</a></li> <li><a href="/wiki/C-C_chemokine_receptor_type_6" title="C-C chemokine receptor type 6">CD196</a></li> <li><a href="/wiki/C-C_chemokine_receptor_type_7" title="C-C chemokine receptor type 7">CD197</a></li> <li><a href="/wiki/CCR8_(gene)" title="CCR8 (gene)">CDw198</a></li> <li><a href="/wiki/CCR9" title="CCR9">CDw199</a></li> <li><a href="/wiki/CD200" title="CD200">CD200</a></li></ul> </div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%;background-color: AntiqueWhite">201–250</th><td class="navbox-list-with-group navbox-list navbox-odd hlist" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><a href="/wiki/Endothelial_protein_C_receptor" title="Endothelial protein C receptor">CD201</a></li> <li><a href="/wiki/TEK_tyrosine_kinase" title="TEK tyrosine kinase">CD202b</a></li> <li><a href="/wiki/MSR1" title="MSR1">CD204</a></li> <li><a href="/wiki/LY75" class="mw-redirect" title="LY75">CD205</a></li> <li><a href="/wiki/Mannose_receptor" title="Mannose receptor">CD206</a></li> <li><a href="/wiki/CD207" class="mw-redirect" title="CD207">CD207</a></li> <li><a href="/wiki/LAMP3" title="LAMP3">CD208</a></li> <li><a href="/wiki/DC-SIGN" title="DC-SIGN">CD209</a></li> <li><i>CDw210</i> <ul><li><a href="/wiki/Interleukin_10_receptor,_alpha_subunit" title="Interleukin 10 receptor, alpha subunit">a</a></li> <li><a href="/wiki/Interleukin_10_receptor,_beta_subunit" title="Interleukin 10 receptor, beta subunit">b</a></li></ul></li> <li><a href="/wiki/Interleukin_12_receptor,_beta_1_subunit" title="Interleukin 12 receptor, beta 1 subunit">CD212</a></li> <li><i>CD213a</i> <ul><li><a href="/wiki/IL13RA1" class="mw-redirect" title="IL13RA1">1</a></li> <li><a href="/wiki/IL13RA2" title="IL13RA2">2</a></li></ul></li> <li><a href="/wiki/IL17RA" title="IL17RA">CD217</a></li> <li><i>CD218</i> (<a href="/wiki/IL18R1" title="IL18R1">a</a></li> <li><a href="/wiki/IL18RAP" title="IL18RAP">b</a>)</li> <li><a href="/wiki/Insulin_receptor" title="Insulin receptor">CD220</a></li> <li><a href="/wiki/Insulin-like_growth_factor_1_receptor" title="Insulin-like growth factor 1 receptor">CD221</a></li> <li><a href="/wiki/Insulin-like_growth_factor_2_receptor" title="Insulin-like growth factor 2 receptor">CD222</a></li> <li><a href="/wiki/LAG3" class="mw-redirect" title="LAG3">CD223</a></li> <li><a href="/wiki/GGT1" class="mw-redirect" title="GGT1">CD224</a></li> <li><a href="/wiki/IFITM1" title="IFITM1">CD225</a></li> <li><a href="/wiki/CD226" title="CD226">CD226</a></li> <li><a href="/wiki/MUC1" class="mw-redirect" title="MUC1">CD227</a></li> <li><a href="/wiki/MFI2" class="mw-redirect" title="MFI2">CD228</a></li> <li><a href="/wiki/LY9" title="LY9">CD229</a></li> <li><a href="/wiki/PRNP" class="mw-redirect" title="PRNP">CD230</a></li> <li><a href="/wiki/Band_3" class="mw-redirect" title="Band 3">CD233</a></li> <li><a href="/wiki/Duffy_antigen_system" title="Duffy antigen system">CD234</a></li> <li><i>CD235</i> <ul><li><a href="/wiki/GYPA" class="mw-redirect" title="GYPA">a</a></li> <li><a href="/wiki/GYPB" title="GYPB">b</a></li></ul></li> <li><a href="/wiki/Glycophorin_C" title="Glycophorin C">CD236</a></li> <li><a href="/wiki/Kell_antigen_system" title="Kell antigen system">CD238</a></li> <li><a href="/wiki/Basal_cell_adhesion_molecule" title="Basal cell adhesion molecule">CD239</a></li> <li><a href="/wiki/RHCE_(gene)" title="RHCE (gene)">CD240CE</a></li> <li><a href="/wiki/RHD_(gene)" title="RHD (gene)">CD240D</a></li> <li><a href="/wiki/RHAG" title="RHAG">CD241</a></li> <li><a href="/wiki/P-glycoprotein" title="P-glycoprotein">CD243</a></li> <li><a href="/wiki/CD244" title="CD244">CD244</a></li> <li><a href="/wiki/Anaplastic_lymphoma_kinase" title="Anaplastic lymphoma kinase">CD246</a></li> <li><a href="/wiki/CD247" class="mw-redirect" title="CD247">CD247</a> - <a href="/wiki/CD248" title="CD248">CD248</a></li> <li><a href="/wiki/Glutamyl_aminopeptidase" title="Glutamyl aminopeptidase">CD249</a></li></ul> </div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%;background-color: AntiqueWhite">251–300</th><td class="navbox-list-with-group navbox-list navbox-even hlist" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><a href="/wiki/OX40L" class="mw-redirect" title="OX40L"> CD252</a></li> <li><a href="/wiki/TRAIL" title="TRAIL">CD253</a></li> <li><a href="/wiki/RANKL" title="RANKL">CD254</a></li> <li><a href="/wiki/TNFSF13" class="mw-redirect" title="TNFSF13">CD256</a></li> <li><a href="/wiki/B-cell_activating_factor" title="B-cell activating factor">CD257</a></li> <li><a href="/wiki/TNFSF14" class="mw-redirect" title="TNFSF14">CD258</a></li> <li><a href="/wiki/TNFRSF10A" class="mw-redirect" title="TNFRSF10A">CD261</a></li> <li><a href="/wiki/TNFRSF10B" class="mw-redirect" title="TNFRSF10B">CD262</a></li> <li><a href="/wiki/TNFRSF10C" class="mw-redirect" title="TNFRSF10C">CD263</a></li> <li><a href="/wiki/TNFRSF10D" class="mw-redirect" title="TNFRSF10D">CD264</a></li> <li><a href="/wiki/RANK" title="RANK">CD265</a></li> <li><a href="/wiki/TNFRSF12A" title="TNFRSF12A">CD266</a></li> <li><a href="/wiki/TNFRSF13B" class="mw-redirect" title="TNFRSF13B">CD267</a></li> <li><a href="/wiki/TNFRSF13C" class="mw-redirect" title="TNFRSF13C">CD268</a></li> <li><a href="/wiki/TNFRSF17" class="mw-redirect" title="TNFRSF17">CD269</a></li> <li><a href="/wiki/Low-affinity_nerve_growth_factor_receptor" title="Low-affinity nerve growth factor receptor">CD271</a></li> <li><a href="/wiki/BTLA" title="BTLA">CD272</a></li> <li><a href="/wiki/PDCD1LG2" title="PDCD1LG2">CD273</a></li> <li><a href="/wiki/CD274" class="mw-redirect" title="CD274">CD274</a></li> <li><a href="/wiki/ICOSLG" title="ICOSLG">CD275</a></li> <li><a href="/wiki/CD276" title="CD276">CD276</a></li> <li><a href="/wiki/CD278" title="CD278">CD278</a></li> <li><a class="mw-selflink selflink">CD279</a></li> <li><a href="/wiki/Mannose_receptor" title="Mannose receptor">CD280</a></li> <li><a href="/wiki/TLR_1" class="mw-redirect" title="TLR 1">CD281</a></li> <li><a href="/wiki/TLR2" class="mw-redirect" title="TLR2">CD282</a></li> <li><a href="/wiki/TLR3" class="mw-redirect" title="TLR3">CD283</a></li> <li><a href="/wiki/TLR4" class="mw-redirect" title="TLR4">CD284</a></li> <li><a href="/wiki/TLR6" class="mw-redirect" title="TLR6">CD286</a></li> <li><a href="/wiki/TLR8" class="mw-redirect" title="TLR8">CD288</a></li> <li><a href="/wiki/TLR9" class="mw-redirect" title="TLR9">CD289</a></li> <li><a href="/wiki/TLR10" class="mw-redirect" title="TLR10">CD290</a></li> <li><a href="/wiki/BMPR1A" title="BMPR1A">CD292</a></li> <li><a href="/wiki/BMPR1B" title="BMPR1B">CDw293</a></li> <li><a href="/wiki/CD294" class="mw-redirect" title="CD294">CD294</a></li> <li><a href="/wiki/Leptin_receptor" title="Leptin receptor">CD295</a></li> <li><a href="/wiki/ART4" title="ART4">CD297</a></li> <li><a href="/wiki/ATP1B3" title="ATP1B3">CD298</a></li> <li><a href="/wiki/CLEC4M" title="CLEC4M">CD299</a></li></ul> </div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%;background-color: AntiqueWhite">301–350</th><td class="navbox-list-with-group navbox-list navbox-odd hlist" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><a href="/wiki/CD300A" title="CD300A">CD300A</a></li> <li><a href="/wiki/CLEC10A" title="CLEC10A">CD301</a></li> <li><a href="/wiki/CD302" title="CD302">CD302</a></li> <li><a href="/wiki/CLEC4C" title="CLEC4C">CD303</a></li> <li><a href="/wiki/Neuropilin" title="Neuropilin">CD304</a></li> <li><a href="/wiki/LAIR1" title="LAIR1">CD305</a></li> <li><a href="/wiki/LAIR2" title="LAIR2">CD306</a></li> <li><a href="/wiki/FCRL5" title="FCRL5">CD307</a></li> <li><a href="/wiki/Kinase_insert_domain_receptor" title="Kinase insert domain receptor">CD309</a></li> <li><a href="/wiki/EMR2" title="EMR2">CD312</a></li> <li><a href="/wiki/NKG2D" title="NKG2D">CD314</a></li> <li><a href="/wiki/PTGFRN" title="PTGFRN">CD315</a></li> <li><a href="/wiki/IGSF8" title="IGSF8">CD316</a></li> <li><a href="/wiki/Tetherin" title="Tetherin">CD317</a></li> <li><a href="/wiki/CDCP1" title="CDCP1">CD318</a></li> <li><a href="/wiki/CD320" title="CD320">CD320</a></li> <li><a href="/wiki/F11_receptor" title="F11 receptor">CD321</a></li> <li><a href="/wiki/JAM2" title="JAM2">CD322</a></li> <li><a href="/wiki/CDH1_(gene)" class="mw-redirect" title="CDH1 (gene)">CD324</a></li> <li><a href="/wiki/CDH2" class="mw-redirect" title="CDH2">CD325</a></li> <li><a href="/wiki/Epithelial_cell_adhesion_molecule" title="Epithelial cell adhesion molecule">CD326</a></li> <li><a href="/wiki/SIGLEC6" title="SIGLEC6">CD327</a></li> <li><a href="/wiki/SIGLEC7" title="SIGLEC7">CD328</a></li> <li><a href="/wiki/SIGLEC9" title="SIGLEC9">CD329</a></li> <li><a href="/wiki/Fibroblast_growth_factor_receptor_1" title="Fibroblast growth factor receptor 1">CD331</a></li> <li><a href="/wiki/Fibroblast_growth_factor_receptor_2" title="Fibroblast growth factor receptor 2">CD332</a></li> <li><a href="/wiki/Fibroblast_growth_factor_receptor_3" title="Fibroblast growth factor receptor 3">CD333</a></li> <li><a href="/wiki/Fibroblast_growth_factor_receptor_4" title="Fibroblast growth factor receptor 4">CD334</a></li> <li><a href="/wiki/NCR1" title="NCR1">CD335</a></li> <li><a href="/wiki/NCR2" title="NCR2">CD336</a></li> <li><a href="/wiki/NCR3" title="NCR3">CD337</a></li> <li><a href="/wiki/ABCG2" title="ABCG2">CD338</a></li> <li><a href="/wiki/JAG1" title="JAG1">CD339</a></li> <li><a href="/wiki/HER2/neu" class="mw-redirect" title="HER2/neu">CD340</a></li> <li><a href="/wiki/FZD4" class="mw-redirect" title="FZD4">CD344</a></li> <li><a href="/wiki/FZD9" class="mw-redirect" title="FZD9">CD349</a></li> <li><a href="/wiki/FZD10" class="mw-redirect" title="FZD10">CD350</a></li></ul> </div></td></tr></tbody></table></div> <div class="navbox-styles"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1129693374" /><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1236075235" /></div><div role="navigation" class="navbox" aria-labelledby="Immunoglobulin_superfamily:_CD28_family_receptors66" style="padding:3px"><table class="nowraplinks mw-collapsible autocollapse navbox-inner" style="border-spacing:0;background:transparent;color:inherit"><tbody><tr><th scope="col" class="navbox-title" colspan="2" style="background:#e7dcc3"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1129693374" /><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1239400231" /><div class="navbar plainlinks hlist navbar-mini"><ul><li class="nv-view"><a href="/wiki/Template:CD28_family_receptors" title="Template:CD28 family receptors"><abbr title="View this template">v</abbr></a></li><li class="nv-talk"><a href="/wiki/Template_talk:CD28_family_receptors" title="Template talk:CD28 family receptors"><abbr title="Discuss this template">t</abbr></a></li><li class="nv-edit"><a href="/wiki/Special:EditPage/Template:CD28_family_receptors" title="Special:EditPage/Template:CD28 family receptors"><abbr title="Edit this template">e</abbr></a></li></ul></div><div id="Immunoglobulin_superfamily:_CD28_family_receptors66" style="font-size:114%;margin:0 4em"><a href="/wiki/Immunoglobulin_superfamily" title="Immunoglobulin superfamily">Immunoglobulin superfamily</a>: <a href="/wiki/CD28_family_receptor" title="CD28 family receptor">CD28 family receptors</a></div></th></tr><tr><th scope="row" class="navbox-group" style="width:1%;background-color: AntiqueWhite">receptors</th><td class="navbox-list-with-group navbox-list navbox-odd hlist" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><a href="/wiki/BTLA" title="BTLA">BTLA</a></li> <li><a href="/wiki/CD28" title="CD28">CD28</a></li> <li><a href="/wiki/CTLA-4" class="mw-redirect" title="CTLA-4">CTLA-4</a></li> <li><a href="/wiki/CD278" title="CD278">ICOS</a></li> <li><a href="/wiki/PD-1" class="mw-redirect" title="PD-1">PD-1</a></li></ul> </div></td></tr></tbody></table></div> <ul><li><a rel="nofollow" class="external text" href="http://bsw3.naist.jp/ishida/?page=1057">What I Talk about When I Talk about the Discovery of PD-1 (Yasumasa Ishida)</a></li> <li><a rel="nofollow" class="external text" href="http://www2.mfour.med.kyoto-u.ac.jp/en/pd-1_project.html">PD-1_Project PD-1 project - Honjo Lab</a></li> <li><a rel="nofollow" class="external text" href="http://www2.mfour.med.kyoto-u.ac.jp/pd-1_project.html">PD-1プロジェクト(in Japanese) - Honjo Lab</a></li></ul>    </div><noscript><img src="https://auth.wikimedia.org/loginwiki/wiki/Special:CentralAutoLogin/start?useformat=desktop&type=1x1&usesul3=1" alt="" width="1" height="1" style="border: none; position: absolute;"></noscript> <div class="printfooter" data-nosnippet="">Retrieved from "<a dir="ltr" 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