The LILR Family Has Immune Cell Activating and Inhibitory Members|Bio-Techne

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Inhibitory Members</h2> <p>The leukocyte immunoglobulin-like receptors (LILRs), also known as Ig-like transcripts (ILTs), are a family of immunoregulatory receptors expressed by a range of hematopoietic cell types, including monocytes, macrophages, dendritic cells, granulocytes, natural killer (NK) cells, T cells, and B cells.<sup>1</sup>The LILR family consists of both stimulatory receptors that belong to the LILRA subfamily (LILRA1-6) and inhibitory receptors that belong to the LILRB subfamily (LILRB1-5). While the LILRA receptors promote immune cell activation by signaling through immunoreceptor tyrosine-based activation motifs (ITAMs), the LILRB receptors inhibit immune cell activation by signaling through immunoreceptor tyrosine-based inhibitory motifs (ITIMs).</p> <p>The LILRB subfamily proteins are human and primate-specific, with paired immunoglobulin-like receptor B (PirB) and gp49B1 being the only mouse receptor orthologs identified to date.<sup>2</sup> Several ligands have been reported for human LILRB1/ILT2 and LILRB2/ILT4 including classical (HLA-A, HLA-B, and HLA-C) and non-classical (HLA-E, HLA-F, and HLA-G) MHC class I molecules, S100A8 and S100A9, and the viral MHC homolog, UL18, for LILRB1/ILT2, and several angiopoietin-like proteins (ANGPTLs), CD1d, myelin-associated glycoprotein (MAG), oligodendrocyte myelin glycoprotein (OMgp), oligomeric beta-amyloid (A beta), and reticulon 4 (RTN4/NOGO) for LILRB2/ILT4.<sup>2</sup> Unlike LILRB2/ILT4, LILRB1/ILT2 requires beta2-microglobulin for binding to HLA ligands.<sup>3, 4</sup> Additionally, LILRB1/ILT2 has been shown to bind more strongly to HLA-G than to classical HLA class I molecules, while LILRB2/ILT4 binds more strongly to ANGPTL proteins than to HLA-G.<sup>2-4</sup> ANGPTL proteins have also been found to interact with both LILRB4 and LILRB5 and HLA-class I has also been reported to be a LILRB5 ligand, but the ligands for LILRB3 have yet to be identified.<sup>2, 5</sup></p> <p>Due to their immunosuppressive properties, members of the LILRB subfamily are considered to be immune checkpoint receptors. Ligands of LILRBs, such as HLA-G can be highly expressed on tumor cells and the interaction of HLA-G with LILRB1 has been shown to inhibit the functions of NK cells, dendritic cells, monocytes/macrophages, T cells, and B cells, allowing tumors to evade immune detection.<sup>1, 6, 7</sup> LILRBs are also up-regulated or expressed on various cancer cell types, as well as on immune cells found in the tumor microenvironment including tumor-associated macrophages (TAMs) and myeloid-derived suppressor cells (MDSCs), and are thought to contribute to tumor growth, angiogenesis, and metastasis.<sup>7</sup> Blockade of LILRB2 in a Lewis lung carcinoma model was shown to enhance anti-tumor immune responses, reduce the numbers of granulocytic MDSCs and regulatory T cells, and inhibit tumor progression both on its own, and to a significantly greater extent when combined with anti-PD-L1 treatment.<sup>8</sup> Taken together, these results suggest that LILRBs may represent future targets for cancer immunotherapy.</p> <p><strong>Bio-Techne offers a complete range of products for immuno-oncology researchers studying the effects of different LILRs, including R&D Systems<sup>TM</sup> bioactive recombinant human proteins and antibodies for all of the LILRB and LILRA subfamily members.</strong></p> <p> </p></div> </div> </div> <div> <div class="paragraph paragraph--type--freeform mb-4 paragraph--view-mode--default"> <div><h3>LILR Family - Products by Molecule</h3> <figure class="responsive-figure-table"><table class="table table-bordered"> <tbody> <tr> <td><a href="/search?keywords=lilra1&common_name=LILRA1/CD85i/LIR-6">LILRA1/CD85i/LIR-6t</a></td> <td><a href="/search?keywords=lilra2&common_name=LILRA2/CD85h/ILT1">LILRA2/CD85h/ILT1</a></td> <td><a href="/search?keywords=lilra3&common_name=LILRA3/CD85e">LILRA3/CD85e</a></td> <td><a href="/search?keywords=lilra4&common_name=LILRA4/CD85g/ILT7">LILRA4/CD85g/ILT7</a></td> <td><a href="/search?keywords=lilra5&common_name=LILRA5/CD85f">LILRA5/CD85f</a></td> <td><a href="/search?keywords=lilra6&common_name=LILRA6/CD85b">LILRA6/CD85bt</a></td> </tr> <tr> <td><a href="/search?keywords=lilrb1&common_name=LILRB1/CD85j/ILT2">LILRB1/CD85j/ILT2</a></td> <td><a href="/search?keywords=lilrb2&common_name=LILRB2/CD85d/ILT4">LILRB2/CD85d/ILT4</a></td> <td><a href="/search?keywords=lilrb3&common_name=LILRB3/CD85a/ILT5">LILRB3/CD85a/ILT5</a></td> <td><a href="/search?keywords=lilrb4&common_name=LILRB4/CD85k/ILT3">LILRB4/CD85k/ILT3</a></td> <td><a href="/search?keywords=lilrb5&common_name=LILRB5/CD85c/LIR-8">LILRB5/CD85c/LIR-8</a></td> <td><a href="/search?keywords=pir-b&common_name=PIR-B">PIR-B</a></td> </tr> </tbody> </table></figure></div> </div> </div> <div> <div class="paragraph paragraph--type--button-row paragraph--view-mode--default"> <div class="row"> <div class="col"> <div class="list-grid-wrap"> <div class="row"> <div class="col-md-4"> <a href="/search?keywords=immunechecktargets&category_attr=Proteins%20and%20Enzymes" class="btn btn-primary" type="link"> Search All Immune Checkpoint Protein Products </a> </div> <div class="col-md-4"> <a href="/reagents/proteins/immune-checkpoint-proteins" class="btn btn-primary" type="link"> Learn About Other Immune Checkpoint Proteins </a> </div> <div class="col-md-4"> <a href="/resources/literature/current-and-emerging-immune-checkpoint-targets-immuno-oncology-research-ebook" class="btn btn-primary" type="link"> Request Our Current and Emerging Immune Checkpoint Targets eBook </a> </div> </div> </div> </div> </div> </div> </div> <div> <div class="paragraph paragraph--type--header"> <div> <div><h3>The Leukocyte Immunoglobulin-like Receptor (LILR) Family Consists of Activating and Inhibitory Members that Can Stimulate or Inhibit Immune Cell Activity</h3></div> </div> </div> </div> <div> <div class="paragraph paragraph--type--full-page-text-with-media mb-4 paragraph--view-mode--default"> <div> <img src="https://resources.bio-techne.com/bio-techne-assets/images/research-areas/lilrb-receptor-illustration.jpg" alt="The LILR family, also known as ILTs, consists of both immune cell stimulatory (LILRA) and inhibitory (LILRB) receptors." loading="lazy" > </div> <div><p><strong>Leukocyte immunoglobulin-like receptors mediate immune cell stimulatory and immune cell inhibitory effects. </strong>Members of the leukocyte immunoglobulin-like receptor family belong to the LILRA or LILRB subfamilies, which have immune cell stimulatory or inhibitory effects, respectively. LILRA and LILRB subfamilies bind to a range of different ligands including MHC class I molecules, angiopoietin (ANGPT) and angiopoietin-like (ANGPTL) proteins, and other proteins as shown in the graphic and described in the text. Interactions between the LILR family proteins and their ligands either promote (LILRA; shown on the left) or inhibit (LILRB; shown on the right) immune cell activation. LILRBs in particular are being investigated as potential therapeutic targets due to their immunosuppressive effects.</p></div> </div> </div> <div> <div class="paragraph paragraph--type--header"> <div> <div><h3>Analysis of the Binding of R&D Systems Recombinant Human LILRB2 and ANGPTL7 Proteins</h3></div> </div> </div> </div> <div> <div class="paragraph paragraph--type--_-2-media-to-text mb-4 paragraph--view-mode--default"> <div class="container-fluid container-wide"> <div class="layout layout--twocol-section layout--twocol-section--50-50"> <div class="layout__region layout__region--first"> <div class="hero-content-wrap"> <div class="field_block:paragraph:2_2_media_to_text:field_indv_media"> <div> <img src="https://resources.bio-techne.com/bio-techne-assets/images/research-areas/angptl7-data.jpg" alt="Analysis of the binding response between R&D Systems Recombinant Human LILRB2 and Recombinant Human ANGPTL7 proteins." loading="lazy" > </div> </div> </div> </div> <div class="layout__region layout__region--second"> <div class="hero-content-wrap"> <div class="field_block:paragraph:2_2_media_to_text:field_lg_sngl_frmtd_text_global"> <div><p><strong>Human Angiopoietin-like 7 (ANGPTL7) Binds to LILRB2/ILT4.</strong> <a href="/p/proteins-enzymes/recombinant-human-lilrb2-cd85d-ilt4-his-tag-protein-cf_8429-t4">Recombinant Human LILRB2/ILT4</a> (R&D Systems, Catalog # 8429-T4) was coated on a plate at 2 μg/mL and the indicated concentrations of <a href="/p/proteins-enzymes/recombinant-human-angiopoietin-like-7-protein_914-an">Recombinant Human Angiopoietin-like 7</a> (R&D Systems, Catalog # 914-AN) were added. Recombinant Human ANGPTL7 bound with an ED<sub>50</sub> of 25-150 ng/mL.</p></div> </div> </div> </div> </div> </div> </div> </div> <div> <div class="paragraph paragraph--type--header"> <div> <div><h3>Analysis of the Binding of R&D Systems Recombinant Human LILRB2 and ANGPTL3 Proteins</h3></div> </div> </div> </div> <div> <div class="paragraph paragraph--type--_-2-media-to-text mb-4 paragraph--view-mode--default"> <div class="container-fluid container-wide"> <div class="layout layout--twocol-section layout--twocol-section--50-50"> <div class="layout__region layout__region--first"> <div class="hero-content-wrap"> <div class="field_block:paragraph:2_2_media_to_text:field_indv_media"> <div> <img src="https://resources.bio-techne.com/bio-techne-assets/images/research-areas/angptl3-data.jpg" alt="Analysis of the binding response between R&D Systems Recombinant Human LILRB2 and Recombinant Human ANGPTL3 proteins." loading="lazy" > </div> </div> </div> </div> <div class="layout__region layout__region--second"> <div class="hero-content-wrap"> <div class="field_block:paragraph:2_2_media_to_text:field_lg_sngl_frmtd_text_global"> <div><p><strong>Human Angiopoietin-like 3 (ANGPTL3) Binds to LILRB2/ILT4.</strong> This ELISA binding assay demonstrates <a href="/p/proteins-enzymes/recombinant-human-angiopoietin-like-3-protein-cf_3829-an">Recombinant Human ANGPTL3</a> (Catalog # <a href="https://www.rndsystems.com/Products/3829-AN">3829-AN</a>) binds to <a href="/p/proteins-enzymes/recombinant-human-lilrb2-cd85d-ilt4-fc-chimera-protein-cf_2078-t4">Recombinant Human LILRB2/CD85d/ILT4</a> (Catalog # <a href="https://www.rndsystems.com/Products/2078-T4">2078-T4</a>) with a Kd = 24 nM.</p></div> </div> </div> </div> </div> </div> </div> </div> <div> <div class="paragraph paragraph--type--freeform mb-4 paragraph--view-mode--default"> <div><h2>Related Resources</h2> <p><a href="/reagents/proteins/immune-checkpoint-proteins"><strong>Immune Checkpoint Proteins Research Products</strong></a></p> <p><strong><a href="/resources/literature/current-and-emerging-immune-checkpoint-targets-immuno-oncology-research-ebook">Current and Emerging Immune Checkpoint Targets for Immuno-Oncology Research eBook</a></strong></p> <p><strong><a href="https://www.rndsystems.com/resources/posters/look-inside-tumor-mechanism-tumor-evasion-and-immunosuppression-tumor" target="_blank">A Look Inside a Tumor: Mechanisms of Tumor Evasion and Immunosuppression in the Tumor Microenvironment Poster</a></strong></p> <p><strong><a href="/research-areas/immuno-oncology">Immuno-Oncology Research Area</a></strong></p> <p><strong><a href="/research-areas/cell-and-gene-therapy">Cell and Gene Therapy Research Area</a></strong></p> <p><strong><a href="https://www.rndsystems.com/pathways/t-cell-co-signaling-pathway-lig-recept-interactions" target="_blank">T Cell Co-Signaling: Ligand-Receptor Interactions Pathway</a></strong></p></div> </div> </div> <div> <div id="accordion" class="paragraph mb-4 paragraph--type--references-container paragraph--view-mode--default"> <div class="card-header"> <a class="" data-toggle="collapse" data-target="#refPara-17431" role="button" aria-expanded="true" aria-controls="refPara-17431"> <h5 class="d-inline">References</h5> </a> </div> <div id="refPara-17431" class="paragraph mb-4 paragraph--type--references-container paragraph--view-mode--default collapse accordion show" aria-controls="refPara-17431"> <ol class="py-3"> <li class="py-2"> <p class="paragraph paragraph--type--individual-reference paragraph--view-mode--default image-and-text-default"> <strong>van der Touw, W.</strong> <em> et al. </em> (2017) <a href="https://www.ncbi.nlm.nih.gov/pubmed/28638976" title="View Abstract" target="_blank" rel="noreferrer"> LILRB receptor-mediated regulation of myeloid cell maturation and function.</a> Cancer Immunol. Immunother. <strong>66</strong>:1079. PMID: 28638976. </p> </li> <li class="py-2"> <p class="paragraph paragraph--type--individual-reference paragraph--view-mode--default image-and-text-default"> <strong>Kang, X.</strong> <em> et al. </em> (2016) <a href="https://www.ncbi.nlm.nih.gov/pubmed/26636629" title="View Abstract" target="_blank" rel="noreferrer"> Inhibitory leukocyte immunoglobulin-like receptors: Immune checkpoint proteins and tumor sustaining factors.</a> Cell Cycle <strong>15</strong>:25. PMID: 26636629. </p> </li> <li class="py-2"> <p class="paragraph paragraph--type--individual-reference paragraph--view-mode--default image-and-text-default"> <strong>Allen, R.L.</strong> <em> et al. </em> (2001) <a href="https://www.ncbi.nlm.nih.gov/pubmed/11698424" title="View Abstract" target="_blank" rel="noreferrer"> Leukocyte receptor complex-encoded immunomodulatory receptors show differing specificity for alternative HLA-B27 structures.</a> J. Immunol. <strong>167</strong>:5543. PMID: 11698424. </p> </li> <li class="py-2"> <p class="paragraph paragraph--type--individual-reference paragraph--view-mode--default image-and-text-default"> <strong>Willcox, B.E.</strong> <em> et al. </em> (2003) <a href="https://www.ncbi.nlm.nih.gov/pubmed/12897781" title="View Abstract" target="_blank" rel="noreferrer"> Crystal structure of HLA-A2 bound to LIR-1, a host and viral major histocompatibility complex receptor.</a> Nat. Immunol. <strong>4</strong>:913. PMID: 12897781. </p> </li> <li class="py-2"> <p class="paragraph paragraph--type--individual-reference paragraph--view-mode--default image-and-text-default"> <strong>Zhang, Z.</strong> <em> et al. </em> (2015) <a href="https://www.ncbi.nlm.nih.gov/pubmed/26098415" title="View Abstract" target="_blank" rel="noreferrer"> The leukocyte immunoglobulin-like receptor family member LILRB5 binds to HLA-class I heavy chains.</a> PLoS One <strong>10</strong>:129063. PMID: 26098415. </p> </li> <li class="py-2"> <p class="paragraph paragraph--type--individual-reference paragraph--view-mode--default image-and-text-default"> <strong>Barkal, A.A.</strong> <em> et al. </em> (2017) <a href="https://www.ncbi.nlm.nih.gov/pubmed/29180808" title="View Abstract" target="_blank" rel="noreferrer"> Engagement of MHC class I by the inhibitory receptor LILRB1 suppresses macrophages and is a target of cancer immunotherapy.</a> Nat. Immunol. <strong>19</strong>:76. PMID: 29180808. </p> </li> <li class="py-2"> <p class="paragraph paragraph--type--individual-reference paragraph--view-mode--default image-and-text-default"> <strong>Zhao, J.</strong> <em> et al. </em> (2019) <a href="https://www.ncbi.nlm.nih.gov/pubmed/31267559" title="View Abstract" target="_blank" rel="noreferrer"> The MHC class I-LILRB1 signalling axis as a promising target in cancer therapy.</a> Scand. J. Immunol. <strong>90</strong>:12804. PMID: 31267559. </p> </li> <li class="py-2"> <p class="paragraph paragraph--type--individual-reference paragraph--view-mode--default image-and-text-default"> <strong>Chen, H-M.</strong> <em> et al. </em> (2018) <a href="https://www.ncbi.nlm.nih.gov/pubmed/30352428" title="View Abstract" target="_blank" rel="noreferrer"> Blocking immunoinhibitory receptor LILRB2 reprograms tumor-associated myeloid cells and promotes antitumor immunity.</a> J. Clin. Invest. <strong>128</strong>:5647. PMID: 30352428. </p> </li> </ol> </div> </div> </div> </div> </div> </article> </div> </div> </section> </main> </div> </div> </div> <div id="brandsbar-footer" class="bg-bt-primary"> <div class="container-wide container-fluid text-white"> <div class="row py-5"> <div class="footer-logo col-xl-3 col-lg-auto d-flex"> <img class="brand-bar-footer-logo" src="/themes/custom/bio_techne_global/logo.svg" alt="Bio-techne logo"> </div> <div class="col-xl-9 col-lg-auto"> <p class="ml-xl-4 bt-px_groteskbold footer-tagline">Global Developer, Manufacturer, and Supplier of High-Quality Reagents, Analytical Instruments, and Precision Diagnostics.</p> </div> <div class="included-brands col"> <span class="font-weight-bold mr-3 bt-inter_regular">INCLUDES</span> <span class="mr-3 bt-inter_regular">R&D Systems™</span> <span class="mr-3 bt-inter_regular">Novus Biologicals™</span> <span class="mr-3 bt-inter_regular">Tocris Bioscience™</span> <span class="mr-3 bt-inter_regular">ProteinSimple™</span> <span 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The LILR Family Has Immune Cell Activating and Inhibitory Members|Bio-Techne