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In the present study, HBcAg-specific, HLA-DR13*-restricted CD4 ؉ Th1-type T-cell clones were generated which secreted both gamma interferon and tumor necrosis factor alpha after in vitro antigen stimulation. These HBcAg-specific CD4 ؉ Th1-type T cells were able to lyse HBc peptide-loaded Epstein-Barr virus-transformed lymphoblastoid target cells in vitro. To examine whether these HLA-DR13*-restricted human CD4 ؉ Th1 T cells also display the same cytotoxic effects in vivo, we transferred peripheral blood leukocytes (PBL) derived from HBV-infected donors or an HBV-naïve donor sharing the DR13*, together with the HBcAg-specific CD4 ؉ Th1-type T","publication_date":"2001,,","publication_name":"Journal of Virology","grobid_abstract_attachment_id":"44465449"},"document_type":"paper","pre_hit_view_count_baseline":null,"quality":"high","language":"en","title":"In Vivo Inhibition of Anti-Hepatitis B Virus Core Antigen (HBcAg) Immunoglobulin G Production by HBcAg-Specific CD4+ Th1-Type T-Cell Clones in a hu-PBL-NOD/SCID Mouse Model","broadcastable":true,"draft":null,"has_indexable_attachment":true,"indexable":true}}["work"]; window.loswp.workCoauthors = [33770610]; window.loswp.locale = "en"; window.loswp.countryCode = "SG"; window.loswp.cwvAbTestBucket = ""; window.loswp.designVariant = "ds_vanilla"; window.loswp.fullPageMobileSutdModalVariant = "control"; window.loswp.useOptimizedScribd4genScript = false; window.loginModal = {}; window.loginModal.appleClientId = 'edu.academia.applesignon';</script><script defer="" src="https://accounts.google.com/gsi/client"></script><div class="ds-loswp-container"><div class="ds-work-card--grid-container"><div class="ds-work-card--container js-loswp-work-card"><div class="ds-work-card--cover"><div class="ds-work-cover--wrapper"><div class="ds-work-cover--container"><button class="ds-work-cover--clickable js-swp-download-button" data-signup-modal="{"location":"swp-splash-paper-cover","attachmentId":44465449,"attachmentType":"pdf"}"><img alt="First page of “In Vivo Inhibition of Anti-Hepatitis B Virus Core Antigen (HBcAg) Immunoglobulin G Production by HBcAg-Specific CD4+ Th1-Type T-Cell Clones in a hu-PBL-NOD/SCID Mouse Model”" class="ds-work-cover--cover-thumbnail" src="https://0.academia-photos.com/attachment_thumbnails/44465449/mini_magick20190214-21059-gkxx0v.png?1550178314" /><img alt="PDF Icon" class="ds-work-cover--file-icon" src="//a.academia-assets.com/images/single_work_splash/adobe_icon.svg" /><div class="ds-work-cover--hover-container"><span class="material-symbols-outlined" style="font-size: 20px" translate="no">download</span><p>Download Free PDF</p></div><div class="ds-work-cover--ribbon-container">Download Free PDF</div><div class="ds-work-cover--ribbon-triangle"></div></button></div></div></div><div class="ds-work-card--work-information"><h1 class="ds-work-card--work-title">In Vivo Inhibition of Anti-Hepatitis B Virus Core Antigen (HBcAg) Immunoglobulin G Production by HBcAg-Specific CD4+ Th1-Type T-Cell Clones in a hu-PBL-NOD/SCID Mouse Model</h1><div class="ds-work-card--work-authors ds-work-card--detail"><a class="ds-work-card--author js-wsj-grid-card-author ds2-5-body-md ds2-5-body-link" data-author-id="33770610" href="https://independent.academia.edu/IsabelleDesombere"><img alt="Profile image of Isabelle Desombere" class="ds-work-card--author-avatar" src="//a.academia-assets.com/images/s65_no_pic.png" />Isabelle Desombere</a></div><div class="ds-work-card--detail"><p class="ds-work-card--detail ds2-5-body-sm">2001, Journal of Virology</p><div class="ds-work-card--work-metadata"><div class="ds-work-card--work-metadata__stat"><span class="material-symbols-outlined" style="font-size: 20px" translate="no">visibility</span><p class="ds2-5-body-sm" id="work-metadata-view-count">…</p></div><div class="ds-work-card--work-metadata__stat"><span class="material-symbols-outlined" style="font-size: 20px" translate="no">description</span><p class="ds2-5-body-sm">8 pages</p></div><div class="ds-work-card--work-metadata__stat"><span class="material-symbols-outlined" style="font-size: 20px" translate="no">link</span><p class="ds2-5-body-sm">1 file</p></div></div><script>(async () => { const workId = 24101187; 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In the present study, HBcAg-specific, HLA-DR13*-restricted CD4 ؉ Th1-type T-cell clones were generated which secreted both gamma interferon and tumor necrosis factor alpha after in vitro antigen stimulation. These HBcAg-specific CD4 ؉ Th1-type T cells were able to lyse HBc peptide-loaded Epstein-Barr virus-transformed lymphoblastoid target cells in vitro. To examine whether these HLA-DR13*-restricted human CD4 ؉ Th1 T cells also display the same cytotoxic effects in vivo, we transferred peripheral blood leukocytes (PBL) derived from HBV-infected donors or an HBV-naïve donor sharing the DR13*, together with the HBcAg-specific CD4 ؉ Th1-type T</p><div class="ds-work-card--button-container"><button class="ds2-5-button js-swp-download-button" data-signup-modal="{"location":"continue-reading-button--work-card","attachmentId":44465449,"attachmentType":"pdf","workUrl":"https://www.academia.edu/24101187/In_Vivo_Inhibition_of_Anti_Hepatitis_B_Virus_Core_Antigen_HBcAg_Immunoglobulin_G_Production_by_HBcAg_Specific_CD4_Th1_Type_T_Cell_Clones_in_a_hu_PBL_NOD_SCID_Mouse_Model"}">See full PDF</button><button class="ds2-5-button ds2-5-button--secondary js-swp-download-button" data-signup-modal="{"location":"download-pdf-button--work-card","attachmentId":44465449,"attachmentType":"pdf","workUrl":"https://www.academia.edu/24101187/In_Vivo_Inhibition_of_Anti_Hepatitis_B_Virus_Core_Antigen_HBcAg_Immunoglobulin_G_Production_by_HBcAg_Specific_CD4_Th1_Type_T_Cell_Clones_in_a_hu_PBL_NOD_SCID_Mouse_Model"}"><span class="material-symbols-outlined" style="font-size: 20px" translate="no">download</span>Download PDF</button></div></div></div></div><div data-auto_select="false" data-client_id="331998490334-rsn3chp12mbkiqhl6e7lu2q0mlbu0f1b" data-doc_id="44465449" data-landing_url="https://www.academia.edu/24101187/In_Vivo_Inhibition_of_Anti_Hepatitis_B_Virus_Core_Antigen_HBcAg_Immunoglobulin_G_Production_by_HBcAg_Specific_CD4_Th1_Type_T_Cell_Clones_in_a_hu_PBL_NOD_SCID_Mouse_Model" data-login_uri="https://www.academia.edu/registrations/google_one_tap" data-moment_callback="onGoogleOneTapEvent" id="g_id_onload"></div><div class="ds-top-related-works--grid-container"><div class="ds-related-content--container ds-top-related-works--container"><h2 class="ds-related-content--heading">Related papers</h2><div class="ds-related-work--container js-wsj-grid-card" data-collection-position="0" data-entity-id="24101185" data-sort-order="default"><a class="ds-related-work--title js-wsj-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/24101185/Hepatitis_B_Virus_Core_Antigen_Binds_and_Activates_Naive_Human_B_Cells_In_Vivo_Studies_with_a_Human_PBL_NOD_SCID_Mouse_Model">Hepatitis B Virus Core Antigen Binds and Activates Naive Human B Cells In Vivo: Studies with a Human PBL-NOD/SCID Mouse Model</a><div class="ds-related-work--metadata"><a class="js-wsj-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="33770610" href="https://independent.academia.edu/IsabelleDesombere">Isabelle Desombere</a></div><p class="ds-related-work--metadata ds2-5-body-xs">Journal of Virology, 2001</p><p class="ds-related-work--abstract ds2-5-body-sm">However, HBcAg-activated hu-PBL from naive donors were unable to switch from IgM to IgG production, even after a booster dose of HBcAg. Production of HBcAg-specific IgG could only be induced when hu-PBL from subjects who had recovered from or had an ongoing chronic HBV infection were transferred into NOD/SCID mice. Our data suggest that humans also have a population of naive B cells that can bind HBcAg and is subsequently activated to produce HBcAg-binding IgM.</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"Hepatitis B Virus Core Antigen Binds and Activates Naive Human B Cells In Vivo: Studies with a Human PBL-NOD/SCID Mouse Model","attachmentId":44465445,"attachmentType":"pdf","work_url":"https://www.academia.edu/24101185/Hepatitis_B_Virus_Core_Antigen_Binds_and_Activates_Naive_Human_B_Cells_In_Vivo_Studies_with_a_Human_PBL_NOD_SCID_Mouse_Model","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-wsj-grid-card-view-pdf" href="https://www.academia.edu/24101185/Hepatitis_B_Virus_Core_Antigen_Binds_and_Activates_Naive_Human_B_Cells_In_Vivo_Studies_with_a_Human_PBL_NOD_SCID_Mouse_Model"><span class="ds2-5-text-link__content">View PDF</span><span class="material-symbols-outlined" style="font-size: 18px" translate="no">chevron_right</span></a></div></div><div class="ds-related-work--container js-wsj-grid-card" data-collection-position="1" data-entity-id="121040072" data-sort-order="default"><a class="ds-related-work--title js-wsj-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/121040072/Activation_of_a_heterogeneous_hepatitis_B_HB_core_and_e_antigen_specific_CD4_T_cell_population_during_seroconversion_to_anti_HBe_and_anti_HBs_in_hepatitis_B_virus_infection">Activation of a heterogeneous hepatitis B (HB) core and e antigen-specific CD4+ T-cell population during seroconversion to anti-HBe and anti-HBs in hepatitis B virus infection</a><div class="ds-related-work--metadata"><a class="js-wsj-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="45725741" href="https://independent.academia.edu/HansKilianWill">Hans Kilian Will</a></div><p class="ds-related-work--metadata ds2-5-body-xs">Journal of Virology, 1995</p><p class="ds-related-work--abstract ds2-5-body-sm">Overcoming hepatitis B virus infection essentially depends on the appropriate immune response of the infected host. Among the hepatitis B virus antigens, the core (HBcAg) and e (HBeAg) proteins appear highly immunogenic and induce important lymphocyte effector functions. In order to investigate the importance of HBcAg/HBeAg-specific T lymphocytes in patients with acute and chronic hepatitis B and to identify immunodominant epitopes within the HBcAg/HBeAg, CD4 ؉ T-cell responses to hepatitis B virus-encoded HBcAg and HBcAg/HBeAg-derived peptides were studied in 49 patients with acute and 39 patients with chronic hepatitis B. The results show a frequent antigen-specific CD4 ؉ T-cell activation during acute hepatitis B infection, a rare HBcAg/HBeAg-specific CD4 ؉ T-cell response among HBeAg ؉ chronic carriers, and no response in patients with anti-HBe ؉ chronic hepatitis. An increasing CD4 ؉ T-cell response to HBcAg/HBeAg coincides with loss of HBeAg and hepatitis B virus surface antigen (HBsAg). Functional analysis of peptide-specific CD4 ؉ T-cell clones revealed a heterogeneous population with respect to lymphokine production. Epitope mapping within the HBcAg/HBeAg peptide defined amino acids (aa) 1 to 25 and aa 61 to 85, irrespective of the HLA haplotype, as the predominant CD4 ؉ T-cell recognition sites. Other important sequences could be identified in the amino-terminal part of the protein, aa 21 to 45, aa 41 to 65, and aa 81 to 105. The immunodominant epitopes are expressed in both proteins, HBcAg and HBeAg. Our findings lead to the conclusion that activation of CD4 ؉ T lymphocytes by HBcAg/HBeAg is a prerequisite for viral elimination, and further studies have to focus on the question of how to enhance or induce this type of T-cell response in chronic carriers. The immunodominant viral sequences identified may have relevance to synthetic vaccine design and to the use of peptide T-cell sites as immunotherapeutic agents in chronic infection.</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"Activation of a heterogeneous hepatitis B (HB) core and e antigen-specific CD4+ T-cell population during seroconversion to anti-HBe and anti-HBs in hepatitis B virus infection","attachmentId":116020433,"attachmentType":"pdf","work_url":"https://www.academia.edu/121040072/Activation_of_a_heterogeneous_hepatitis_B_HB_core_and_e_antigen_specific_CD4_T_cell_population_during_seroconversion_to_anti_HBe_and_anti_HBs_in_hepatitis_B_virus_infection","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-wsj-grid-card-view-pdf" href="https://www.academia.edu/121040072/Activation_of_a_heterogeneous_hepatitis_B_HB_core_and_e_antigen_specific_CD4_T_cell_population_during_seroconversion_to_anti_HBe_and_anti_HBs_in_hepatitis_B_virus_infection"><span class="ds2-5-text-link__content">View PDF</span><span class="material-symbols-outlined" style="font-size: 18px" translate="no">chevron_right</span></a></div></div><div class="ds-related-work--container js-wsj-grid-card" data-collection-position="2" data-entity-id="27418302" data-sort-order="default"><a class="ds-related-work--title js-wsj-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/27418302/Improving_on_the_Ability_of_Endogenous_Hepatitis_B_Core_Antigen_to_Prime_Cytotoxic_T_Lymphocytes">Improving on the Ability of Endogenous Hepatitis B Core Antigen to Prime Cytotoxic T Lymphocytes</a><div class="ds-related-work--metadata"><a class="js-wsj-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="34830291" href="https://independent.academia.edu/LFrelin">L. Frelin</a></div><p class="ds-related-work--metadata ds2-5-body-xs">The Journal of Infectious Diseases, 2010</p><p class="ds-related-work--abstract ds2-5-body-sm">Hepatitis B virus core antigen (HBcAg) is thought to be a key target for the host immune response in controlling the infection [1]. In particular, the presence of HBcAg-specific T cells has been associated with clearance of acute and chronic hepatitis B virus infections . Subsequently, prophylactic and therapeutic vaccines that induce HBcAg-specific T cells have been developed and have shown some efficiency in infectious models . However, despite the high immunogenicity of exogenous HBcAg, findings have been disappointing in many of the studies using endogenous HBcAg as a vaccine.</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"Improving on the Ability of Endogenous Hepatitis B Core Antigen to Prime Cytotoxic T Lymphocytes","attachmentId":47674890,"attachmentType":"pdf","work_url":"https://www.academia.edu/27418302/Improving_on_the_Ability_of_Endogenous_Hepatitis_B_Core_Antigen_to_Prime_Cytotoxic_T_Lymphocytes","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-wsj-grid-card-view-pdf" href="https://www.academia.edu/27418302/Improving_on_the_Ability_of_Endogenous_Hepatitis_B_Core_Antigen_to_Prime_Cytotoxic_T_Lymphocytes"><span class="ds2-5-text-link__content">View PDF</span><span class="material-symbols-outlined" style="font-size: 18px" translate="no">chevron_right</span></a></div></div><div class="ds-related-work--container js-wsj-grid-card" data-collection-position="3" data-entity-id="22468026" data-sort-order="default"><a class="ds-related-work--title js-wsj-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/22468026/Induction_of_anti_hepatitis_B_surface_antigen_HBsAg_antibodies_in_HBsAg_producing_transgenic_mice_A_possible_way_of_circumventing_nonresponse_to_HBsAg">Induction of anti-hepatitis B surface antigen (HBsAg) antibodies in HBsAg producing transgenic mice: A possible way of circumventing “nonresponse” to HBsAg</a><div class="ds-related-work--metadata"><a class="js-wsj-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="32724872" href="https://pasteur.academia.edu/MarielouiseMichel">Marie-louise Michel</a><span>, </span><a class="js-wsj-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="13529286" href="https://inserm.academia.edu/michellehadchouel">michelle hadchouel</a></div><p class="ds-related-work--metadata ds2-5-body-xs">Journal of Medical Virology, 1993</p><p class="ds-related-work--abstract ds2-5-body-sm">Paris Cedex 15 (M.M., P.T., C.P., M.-L.M.), and Hepatologie Pediatrique, Hopital de BicGtre, 94275 Le Kremlin BicGtre (M.H.), France</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"Induction of anti-hepatitis B surface antigen (HBsAg) antibodies in HBsAg producing transgenic mice: A possible way of circumventing “nonresponse” to HBsAg","attachmentId":43088678,"attachmentType":"pdf","work_url":"https://www.academia.edu/22468026/Induction_of_anti_hepatitis_B_surface_antigen_HBsAg_antibodies_in_HBsAg_producing_transgenic_mice_A_possible_way_of_circumventing_nonresponse_to_HBsAg","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-wsj-grid-card-view-pdf" href="https://www.academia.edu/22468026/Induction_of_anti_hepatitis_B_surface_antigen_HBsAg_antibodies_in_HBsAg_producing_transgenic_mice_A_possible_way_of_circumventing_nonresponse_to_HBsAg"><span class="ds2-5-text-link__content">View PDF</span><span class="material-symbols-outlined" style="font-size: 18px" translate="no">chevron_right</span></a></div></div><div class="ds-related-work--container js-wsj-grid-card" data-collection-position="4" data-entity-id="90960450" data-sort-order="default"><a class="ds-related-work--title js-wsj-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/90960450/Recombinant_HBsAg_of_the_Wild_Type_and_the_G145R_Escape_Mutant_included_in_the_New_Multivalent_Vaccine_against_Hepatitis_B_Virus_Dramatically_Differ_in_their_Effects_on_Leukocytes_from_Healthy_Donors_In_Vitro">Recombinant HBsAg of the Wild-Type and the G145R Escape Mutant, included in the New Multivalent Vaccine against Hepatitis B Virus, Dramatically Differ in their Effects on Leukocytes from Healthy Donors In Vitro</a><div class="ds-related-work--metadata"><a class="js-wsj-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="70185350" href="https://independent.academia.edu/%D0%90%D0%BD%D0%B0%D1%82%D0%BE%D0%BB%D0%B8%D0%B9%D0%A1%D1%83%D1%81%D0%BB%D0%BE%D0%B2">Анатолий Суслов</a></div><p class="ds-related-work--metadata ds2-5-body-xs">Vaccines, 2022</p><p class="ds-related-work--abstract ds2-5-body-sm">Immune-escape hepatitis B virus (HBV) mutants play an important role in HBV spread. Recently, the multivalent vaccine Bubo®-Unigep has been developed to protect against both wild-type HBV and the most significant G145R mutant. Here, we compared the effects of recombinant HBsAg antigens, wild-type and mutated at G145R, both included in the new vaccine, on activation of a human high-density culture of peripheral blood mononuclear cells (PBMC) in vitro. The antigens were used either alone or in combination with phytohemagglutinin (PHA). None of the antigens alone affected the expression of CD40, HLA-DR or CD279. Wild-type HBsAg enhanced CD86 and CD69 expression, and induced TNF-α, IL-10, and IFN-γ, regardless of the anti-HBsAg status of donor. In the presence of PHA, wild-type HBsAg had no effect on either of the tested surface markers, but increased IFN-γ and IL-10 and inhibited IL-2. In contrast, the G145R mutant alone did not affect CD86 expression, it induced less CD69, and stimula...</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"Recombinant HBsAg of the Wild-Type and the G145R Escape Mutant, included in the New Multivalent Vaccine against Hepatitis B Virus, Dramatically Differ in their Effects on Leukocytes from Healthy Donors In Vitro","attachmentId":94380222,"attachmentType":"pdf","work_url":"https://www.academia.edu/90960450/Recombinant_HBsAg_of_the_Wild_Type_and_the_G145R_Escape_Mutant_included_in_the_New_Multivalent_Vaccine_against_Hepatitis_B_Virus_Dramatically_Differ_in_their_Effects_on_Leukocytes_from_Healthy_Donors_In_Vitro","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-wsj-grid-card-view-pdf" href="https://www.academia.edu/90960450/Recombinant_HBsAg_of_the_Wild_Type_and_the_G145R_Escape_Mutant_included_in_the_New_Multivalent_Vaccine_against_Hepatitis_B_Virus_Dramatically_Differ_in_their_Effects_on_Leukocytes_from_Healthy_Donors_In_Vitro"><span class="ds2-5-text-link__content">View PDF</span><span class="material-symbols-outlined" style="font-size: 18px" translate="no">chevron_right</span></a></div></div><div class="ds-related-work--container js-wsj-grid-card" data-collection-position="5" data-entity-id="11210973" data-sort-order="default"><a class="ds-related-work--title js-wsj-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/11210973/Impact_of_the_Immunogen_Nature_on_the_Immune_Response_against_the_Major_HBV_Antigens_in_an_HBsAg_and_HLA_humanized_Transgenic_Mouse_Model">Impact of the Immunogen Nature on the Immune Response against the Major HBV Antigens in an HBsAg and HLA-humanized Transgenic Mouse Model</a><div class="ds-related-work--metadata"><a class="js-wsj-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="27089342" href="https://independent.academia.edu/JosimarGuillenAguilar">Josimar Guillen Aguilar</a></div><p class="ds-related-work--metadata ds2-5-body-xs">Euroasian Journal of Hepato-Gastroenterology, 2014</p><p class="ds-related-work--abstract ds2-5-body-sm">In conclusion, our results indicate that cellular immune responses necessary for the development of protective immunity can be achieved by DNA or protein immunization. However, important differences in their nature arise when immunogens are administered several times.</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"Impact of the Immunogen Nature on the Immune Response against the Major HBV Antigens in an HBsAg and HLA-humanized Transgenic Mouse Model","attachmentId":46817511,"attachmentType":"pdf","work_url":"https://www.academia.edu/11210973/Impact_of_the_Immunogen_Nature_on_the_Immune_Response_against_the_Major_HBV_Antigens_in_an_HBsAg_and_HLA_humanized_Transgenic_Mouse_Model","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-wsj-grid-card-view-pdf" href="https://www.academia.edu/11210973/Impact_of_the_Immunogen_Nature_on_the_Immune_Response_against_the_Major_HBV_Antigens_in_an_HBsAg_and_HLA_humanized_Transgenic_Mouse_Model"><span class="ds2-5-text-link__content">View PDF</span><span class="material-symbols-outlined" style="font-size: 18px" translate="no">chevron_right</span></a></div></div><div class="ds-related-work--container js-wsj-grid-card" data-collection-position="6" data-entity-id="6416696" data-sort-order="default"><a class="ds-related-work--title js-wsj-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/6416696/Priming_of_cytotoxic_T_cell_responses_to_exogenous_hepatitis_B_virus_core_antigen_is_B_cell_dependent">Priming of cytotoxic T cell responses to exogenous hepatitis B virus core antigen is B cell dependent</a><div class="ds-related-work--metadata"><a class="js-wsj-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="50126601" href="https://independent.academia.edu/IrinaSominskaya">Irina Sominskaya</a><span>, </span><a class="js-wsj-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="65933966" href="https://independent.academia.edu/DCroninhennessy">David R Milich</a><span>, </span><a class="js-wsj-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="10099295" href="https://lu-lv.academia.edu/PaulPumpens">Paul Pumpens</a></div><p class="ds-related-work--metadata ds2-5-body-xs">Journal of General Virology, 2003</p><p class="ds-related-work--abstract ds2-5-body-sm">The hepatitis B virus (HBV) core antigen (HBcAg) has a unique ability to bind a high frequency of naive human and murine B cells. The role of HBcAg-binding naive B cells in the immunogenicity of HBcAg is not clear. The HBcAg-binding properties of naive B cells were characterized using HBcAg particles with mutated spike region (residues 76-85) sequences. Deletion of residues 76-85 (HBcD76-85) destroyed naive B cell binding, whereas deletion of residues 79-85 did not. HBcAg particles with an Ile instead of the natural Ala at position 80 did not bind naive B cells, whereas reversion of Ile 80 RAla restored B cell binding. Destroying the B cell-binding ability of HBcAg had a marginal effect on the overall B cell immunogenicity of the different particles, suggesting that they were equally efficient in priming T helper cells. Therefore, the importance of HBcAg-binding B cells is studied with relation to the priming of HBcAg-specific cytotoxic T cells (CTLs). The role of HBcAg-binding B cells in the priming of HBcAg-specific CTLs was evaluated by immunization with endogenous HBcAg (DNA immunization) and exogenous recombinant HBcAg particles. Endogenous HBcAg primed HBcAg-specific CTLs in wild-type and B cell-deficient mice, whereas exogenous HBcAg primed HBcAg-specific CTLs only in wild-type mice. Importantly, HBcD76-85 did not prime CTLs despite the presence of B cells. Thus, the ability of exogenous HBcAg particles to prime specific CTLs is B cell dependent, suggesting a possible role for HBcAgbinding B cells in HBV infections.</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"Priming of cytotoxic T cell responses to exogenous hepatitis B virus core antigen is B cell dependent","attachmentId":33221512,"attachmentType":"pdf","work_url":"https://www.academia.edu/6416696/Priming_of_cytotoxic_T_cell_responses_to_exogenous_hepatitis_B_virus_core_antigen_is_B_cell_dependent","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-wsj-grid-card-view-pdf" href="https://www.academia.edu/6416696/Priming_of_cytotoxic_T_cell_responses_to_exogenous_hepatitis_B_virus_core_antigen_is_B_cell_dependent"><span class="ds2-5-text-link__content">View PDF</span><span class="material-symbols-outlined" style="font-size: 18px" translate="no">chevron_right</span></a></div></div><div class="ds-related-work--container js-wsj-grid-card" data-collection-position="7" data-entity-id="11468322" data-sort-order="default"><a class="ds-related-work--title js-wsj-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/11468322/Modulation_of_the_immunological_response_to_hepatitis_b_virus_by_antibodies">Modulation of the immunological response to hepatitis b virus by antibodies</a><div class="ds-related-work--metadata"><a class="js-wsj-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="27925195" href="https://independent.academia.edu/KatalinAbraham">Katalin Abraham</a></div><p class="ds-related-work--metadata ds2-5-body-xs">Hepatology, 1987</p><p class="ds-related-work--abstract ds2-5-body-sm">Antibodies to HBsAg of IgG class enhanced the helper activity of a human T cell clone to promote the in vitro synthesis of immunoglobulins by autologous B lymphocytes. Using two different assay systems, the effect of antigen-epecific antibodies on the helper function of a EBsAg-reactive T cell clone was studied. The monoclonal antibody to HBsAg ASC3 (IgG) increased significantly the T cell-dependent production of immunoglobulins by Staphyloccocus aureus-stimulated autologous B lymphocytee. Furthermore, the results obtained with a different type of assay showed that ASC3 also increased the synthesis of antibody to HBsAg by the autologous B cells in the presence of HBsAg and the helper T cell clone. On the other hand, when the monoclonal antibody to EBsAg of IgM class, H5D3 or the F(ab% fragment of A5C3 were tested, no significant enhancement of the</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"Modulation of the immunological response to hepatitis b virus by antibodies","attachmentId":46690794,"attachmentType":"pdf","work_url":"https://www.academia.edu/11468322/Modulation_of_the_immunological_response_to_hepatitis_b_virus_by_antibodies","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-wsj-grid-card-view-pdf" href="https://www.academia.edu/11468322/Modulation_of_the_immunological_response_to_hepatitis_b_virus_by_antibodies"><span class="ds2-5-text-link__content">View PDF</span><span class="material-symbols-outlined" style="font-size: 18px" translate="no">chevron_right</span></a></div></div><div class="ds-related-work--container js-wsj-grid-card" data-collection-position="8" data-entity-id="100153273" data-sort-order="default"><a class="ds-related-work--title js-wsj-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/100153273/HBsAg_redirected_T_cells_exhibit_antiviral_activity_in_HBV_infected_human_liver_chimeric_mice">HBsAg-redirected T cells exhibit antiviral activity in HBV-infected human liver chimeric mice</a><div class="ds-related-work--metadata"><a class="js-wsj-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="219434259" href="https://independent.academia.edu/bbissigchoisat">beatrice bissig-choisat</a></div><p class="ds-related-work--metadata ds2-5-body-xs">Cytotherapy, 2018</p><p class="ds-related-work--abstract ds2-5-body-sm">Chronic hepatitis B virus (HBV) infection remains incurable. Although HBsAg-specific chimeric antigen receptor (HBsAg-CAR) T cells have been generated, they have not been tested in animal models with authentic HBV infection. We generated a novel CAR targeting HBsAg and evaluated its ability to recognize HBV+ cell lines and HBsAg particles in vitro. In vivo, we tested whether human HBsAg-CAR T cells would have efficacy against HBV-infected hepatocytes in human liver chimeric mice. HBsAg-CAR T cells recognized HBV-positive cell lines and HBsAg particles in vitro as judged by cytokine production. However, HBsAg-CAR T cells did not kill HBV-positive cell lines in cytotoxicity assays. Adoptive transfer of HBsAg-CAR T cells into HBV-infected humanized mice resulted in accumulation within the liver and a significant decrease in plasma HBsAg and HBV-DNA levels compared with control mice. Notably, the fraction of HBV core-positive hepatocytes among total human hepatocytes was greatly reduced...</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"HBsAg-redirected T cells exhibit antiviral activity in HBV-infected human liver chimeric mice","attachmentId":101055043,"attachmentType":"pdf","work_url":"https://www.academia.edu/100153273/HBsAg_redirected_T_cells_exhibit_antiviral_activity_in_HBV_infected_human_liver_chimeric_mice","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-wsj-grid-card-view-pdf" href="https://www.academia.edu/100153273/HBsAg_redirected_T_cells_exhibit_antiviral_activity_in_HBV_infected_human_liver_chimeric_mice"><span class="ds2-5-text-link__content">View PDF</span><span class="material-symbols-outlined" style="font-size: 18px" translate="no">chevron_right</span></a></div></div><div class="ds-related-work--container js-wsj-grid-card" data-collection-position="9" data-entity-id="60836796" data-sort-order="default"><a class="ds-related-work--title js-wsj-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/60836796/Immunoprevalence_and_Immunodominance_of_HLA_Cw_0801_Restricted_T_Cell_Response_Targeting_the_Hepatitis_B_Virus_Envelope_Transmembrane_Region">Immunoprevalence and Immunodominance of HLA-Cw*0801-Restricted T Cell Response Targeting the Hepatitis B Virus Envelope Transmembrane Region</a><div class="ds-related-work--metadata"><a class="js-wsj-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="19168940" href="https://nus.academia.edu/NasirahBanu">Nasirah Banu</a></div><p class="ds-related-work--metadata ds2-5-body-xs">Journal of Virology, 2014</p><p class="ds-related-work--abstract ds2-5-body-sm">HLA-C-restricted T cells have been shown to play an important role in HIV control, but their impact on protection or pathogenesis in other viral infections remains elusive. Here, we characterized the hierarchy of HLA class I-restricted hepatitis B virus (HBV) epitopes targeted by CD8 T cells in HBV-infected subjects. The frequency of CD8 T cells specific for a panel of 18 HBV epitopes (restricted by HLA-A‫70/30/1020ء‬ [hereinafter HLA-A0201/03/07],-A1101,-A2402/07,-B5801,-B4001,-B1301, and-Cw0801) was quantified in a total of 59 subjects who resolved HBV infection. We found that the HLA-Cw0801-restricted epitope comprised of Env residues 171 to 180 (Env 171-180) is immunoprevalent in the Southeast Asian subjects (10/17 HLA-Cw0801-positive subjects) and immunodominant in the majority of HLA-Cw0801-positive subjects able to control HBV infection. HLA-Cw0801-restricted Env 171-180-specific CD8 T cells recognized endogenously produced HBV surface antigen (HBsAg) and tolerated amino acid variations within the epitope detected in HBV genotypes B and C. In conclusion, we demonstrate that the HLA-Cw0801-restricted Env 171-180 T cell response is an important component of the HBV-specific adaptive T cell immunity in Asians infected with HBV. Thus, HLA-C restricted T cells might play an important role in various viral infections.</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"Immunoprevalence and Immunodominance of HLA-Cw*0801-Restricted T Cell Response Targeting the Hepatitis B Virus Envelope Transmembrane Region","attachmentId":74106726,"attachmentType":"pdf","work_url":"https://www.academia.edu/60836796/Immunoprevalence_and_Immunodominance_of_HLA_Cw_0801_Restricted_T_Cell_Response_Targeting_the_Hepatitis_B_Virus_Envelope_Transmembrane_Region","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-wsj-grid-card-view-pdf" href="https://www.academia.edu/60836796/Immunoprevalence_and_Immunodominance_of_HLA_Cw_0801_Restricted_T_Cell_Response_Targeting_the_Hepatitis_B_Virus_Envelope_Transmembrane_Region"><span class="ds2-5-text-link__content">View PDF</span><span class="material-symbols-outlined" style="font-size: 18px" translate="no">chevron_right</span></a></div></div></div></div><div class="ds-sticky-ctas--wrapper js-loswp-sticky-ctas hidden"><div class="ds-sticky-ctas--grid-container"><div class="ds-sticky-ctas--container"><button class="ds2-5-button js-swp-download-button" data-signup-modal="{"location":"continue-reading-button--sticky-ctas","attachmentId":44465449,"attachmentType":"pdf","workUrl":null}">See full PDF</button><button class="ds2-5-button ds2-5-button--secondary js-swp-download-button" data-signup-modal="{"location":"download-pdf-button--sticky-ctas","attachmentId":44465449,"attachmentType":"pdf","workUrl":null}"><span class="material-symbols-outlined" style="font-size: 20px" translate="no">download</span>Download PDF</button></div></div></div><div class="ds-below-fold--grid-container"><div class="ds-work--container js-loswp-embedded-document"><div class="attachment_preview" data-attachment="Attachment_44465449" style="display: none"><div class="js-scribd-document-container"><div class="scribd--document-loading js-scribd-document-loader" style="display: block;"><img alt="Loading..." src="//a.academia-assets.com/images/loaders/paper-load.gif" /><p>Loading Preview</p></div></div><div style="text-align: center;"><div class="scribd--no-preview-alert js-preview-unavailable"><p>Sorry, preview is currently unavailable. 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js-related-work-grid-card-view-pdf" href="https://www.academia.edu/21404183/Mutant_hepatitis_B_virus_surface_antigens_HBsAg_are_immunogenic_but_may_have_a_changed_specificity"><span class="ds2-5-text-link__content">View PDF</span><span class="material-symbols-outlined" style="font-size: 18px" translate="no">chevron_right</span></a></div></div><div class="ds-related-work--container js-related-work-sidebar-card" data-collection-position="6" data-entity-id="32354967" data-sort-order="default"><a class="ds-related-work--title js-related-work-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/32354967/DNA_Mediated_Immunization_in_Mice_Induces_a_Potent_MHC_Class_I_Restricted_Cytotoxic_T_Lymphocyte_Response_to_the_Hepatitis_B_Envelope_Protein">DNA-Mediated Immunization in Mice Induces a Potent MHC Class I-Restricted Cytotoxic T Lymphocyte Response to the Hepatitis B Envelope Protein</a><div class="ds-related-work--metadata"><a class="js-related-work-grid-card-author 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class="ds-related-work--metadata"><a class="js-related-work-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="248818585" href="https://independent.academia.edu/FazleAkbar">Fazle Akbar</a></div><p class="ds-related-work--metadata ds2-5-body-xs">Immunology, 1996</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"Upregulation of MHC class II antigen on dendritic cells from hepatitis B virus transgenic mice by interferon‐γ: abrogation of immune response defect to a T‐cell‐dependent antigen","attachmentId":101310525,"attachmentType":"pdf","work_url":"https://www.academia.edu/100504950/Upregulation_of_MHC_class_II_antigen_on_dendritic_cells_from_hepatitis_B_virus_transgenic_mice_by_interferon_%CE%B3_abrogation_of_immune_response_defect_to_a_T_cell_dependent_antigen","alternativeTracking":true}"><span class="material-symbols-outlined" 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href="https://www.academia.edu/10611084/Hepatitis_B_virus_core_antigen_epitopes_presented_by_HLA_A2_single_chain_trimers_induce_functional_epitope_specific_CD8_T_cell_responses_in_HLA_A2_1_Kb_transgenic_mice">Hepatitis B virus core antigen epitopes presented by HLA-A2 single-chain trimers induce functional epitope-specific CD8 + T-cell responses in HLA-A2�1/Kb transgenic mice</a><div class="ds-related-work--metadata"><a class="js-related-work-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="25926412" href="https://independent.academia.edu/YuxiaZhang">Yuxia Zhang</a></div><p class="ds-related-work--metadata ds2-5-body-xs">Immunology, 2007</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"Hepatitis B virus core antigen epitopes presented by HLA-A2 single-chain trimers induce functional epitope-specific CD8 + T-cell responses in 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class="js-related-work-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="38966386" href="https://independent.academia.edu/ShilpaChokshi">Shilpa Chokshi</a><span>, </span><a class="js-related-work-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="35084352" href="https://independent.academia.edu/MuntherHussain">Munther Hussain</a><span>, </span><a class="js-related-work-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="39155866" href="https://independent.academia.edu/DavidRowlands3">David J Rowlands</a></div><p class="ds-related-work--metadata ds2-5-body-xs">Hepatology, 1995</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"Induction of T-helper cell response to hepatitis B core antigen in chronic hepatitis B: A major factor in activation of the host immune response to the hepatitis B 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data-collection-position="17" data-entity-id="69822530" data-sort-order="default"><a class="ds-related-work--title js-related-work-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/69822530/Priming_Hepatitis_B_Surface_Hbsag_and_Core_Antigen_Hbcag_Specific_Immune_Responses_by_Chimeric_Hbcag_with_a_Hbsag_A_Determinant">Priming Hepatitis B Surface (Hbsag)- and Core Antigen (Hbcag)-Specific Immune Responses by Chimeric, Hbcag with a Hbsag ‘A’ Determinant</a><div class="ds-related-work--metadata"><a class="js-related-work-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="15245382" href="https://independent.academia.edu/NShahrokhi">Nader Shahrokhi</a></div><p class="ds-related-work--metadata ds2-5-body-xs">2006</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"Priming Hepatitis B Surface (Hbsag)- and Core 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