{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,20]],"date-time":"2026-02-20T00:54:19Z","timestamp":1771548859259,"version":"3.50.1"},"reference-count":51,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2008,1,24]],"date-time":"2008-01-24T00:00:00Z","timestamp":1201132800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2008,1,24]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>HBs antigen (HBsAg)183\u2013191 (FLLTRILTI, R187 peptide) is a dominant human leucocyte antigen-A2 (HLA-A2)-restricted epitope associated with hepatitis B virus (HBV) infection in Caucasian populations. However, its prevalence is poorly understood in China, where there is a high incidence of HBV infection. In this report, we sequenced the region of HBsAg derived from 103 Chinese patients. Approximately 16\u00b75% of the patients bore a mutant HBsAg183\u2013191 epitope in which the original arginine (R187) was substituted with a lysine (K187 mutant peptide). Importantly, K187 still bound to HLA-A2 with high affinity, and elicited specific cytotoxic T lymphocyte (CTL) responses in HLA-A2\/Kb transgenic mice. K187-specific CTLs were also generated successfully in acute hepatitis B (AHB) patients, indicating that this mutant epitope is processed and presented effectively. Our findings show that R187-specific CTLs can cross-react with the K187 peptide. These findings reveal that K187 still has the property of an HLA-A2 restricted epitope, and elicits a protective anti-HBV CTL response in humans.<\/jats:p>","DOI":"10.1111\/j.1365-2249.2007.03570.x","type":"journal-article","created":{"date-parts":[[2010,7,27]],"date-time":"2010-07-27T10:58:57Z","timestamp":1280228337000},"page":"441-447","source":"Crossref","is-referenced-by-count":13,"title":["A mutant HBs antigen (HBsAg)183\u2013191 epitope elicits specific cytotoxic T lymphocytes in acute hepatitis B patients"],"prefix":"10.1093","volume":"151","author":[{"given":"H-G","family":"Liu","sequence":"first","affiliation":[{"name":"Center for Molecular Virology, Institute of Microbiology, Chinese Academy of Sciences"},{"name":"Graduate University of Chinese Academy of Sciences, Beijing, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Z-P","family":"Fan","sequence":"additional","affiliation":[{"name":"Research Center for Biological Therapy, Beijing 302 Hospital, Beijing Institute of Infectious Diseases"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"W-W","family":"Chen","sequence":"additional","affiliation":[{"name":"Research Center for Biological Therapy, Beijing 302 Hospital, Beijing Institute of Infectious Diseases"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"H-Y","family":"Yang","sequence":"additional","affiliation":[{"name":"Research Center for Biological Therapy, Beijing 302 Hospital, Beijing Institute of Infectious Diseases"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Q-F","family":"Liu","sequence":"additional","affiliation":[{"name":"Research Center for Biological Therapy, Beijing 302 Hospital, Beijing Institute of Infectious Diseases"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"H","family":"Zhang","sequence":"additional","affiliation":[{"name":"Research Center for Biological Therapy, Beijing 302 Hospital, Beijing Institute of Infectious Diseases"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"P","family":"Tien","sequence":"additional","affiliation":[{"name":"Center for Molecular Virology, Institute of Microbiology, Chinese Academy of Sciences"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"F-S","family":"Wang","sequence":"additional","affiliation":[{"name":"Center for Molecular Virology, Institute of Microbiology, Chinese Academy of Sciences"},{"name":"Research Center for Biological Therapy, Beijing 302 Hospital, Beijing Institute of Infectious Diseases"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2008,1,24]]},"reference":[{"key":"2022010406282150500_b1","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1146\/annurev.iy.13.040195.000333","article-title":"Hepatitis B virus immunopathogenesis","volume":"13","author":"Chisari","year":"1995","journal-title":"Annu Rev Immunology"},{"key":"2022010406282150500_b2","doi-asserted-by":"crossref","first-page":"922","DOI":"10.1016\/S0168-8278(01)00048-4","article-title":"Identification of hepatitis B virus-specific CTL epitopes presented by HLA-A*2402, the most common HLA class I allele in East Asia","volume":"34","author":"Sobao","year":"2001","journal-title":"J Hepatol"},{"key":"2022010406282150500_b3","doi-asserted-by":"crossref","first-page":"7860","DOI":"10.1128\/JVI.79.12.7860-7867.2005","article-title":"T cells with a CD4+CD25+ regulatory phenotype suppress in vitro proliferation of virus-specific CD8+ T cells during chronic hepatitis C virus infection","volume":"79","author":"Boettler","year":"2005","journal-title":"J Virol"},{"key":"2022010406282150500_b4","doi-asserted-by":"crossref","first-page":"1047","DOI":"10.1084\/jem.181.3.1047","article-title":"The cytotoxic T lymphocyte response to multiple hepatitis B virus polymerase epitopes during and after acute viral hepatitis","volume":"181","author":"Rehermann","year":"1995","journal-title":"J Exp Med"},{"key":"2022010406282150500_b5","doi-asserted-by":"crossref","first-page":"1117","DOI":"10.1053\/jhep.2000.19324","article-title":"Incubation phase of acute hepatitis B in man: dynamic of cellular immune mechanisms","volume":"32","author":"Webster","year":"2000","journal-title":"Hepatology"},{"key":"2022010406282150500_b6","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1111\/j.1600-0676.1998.tb00825.x","article-title":"Quantitative and functional analysis of core-specific T-helper cell and CTL activities in acute and chronic hepatitis B","volume":"18","author":"Lohr","year":"1998","journal-title":"Liver"},{"key":"2022010406282150500_b7","first-page":"232","article-title":"Molecular biological features and clinical significance of hepatitis B virus genotype in Nanjin","volume":"4","author":"Zhang","year":"2004","journal-title":"World J Infect"},{"key":"2022010406282150500_b8","first-page":"1347","article-title":"A study on the relationship between HBV genotype and outcome of hepatitis B virus infection","volume":"6","author":"Yan","year":"2004","journal-title":"J Chin Physicians"},{"key":"2022010406282150500_b9","doi-asserted-by":"crossref","first-page":"643","DOI":"10.1046\/j.1440-1746.2002.02737.x","article-title":"Hepatitis B viral genotypes: clinical relevance and molecular characteristics","volume":"17","author":"Kao","year":"2002","journal-title":"J Gastroenterol Hepatol"},{"key":"2022010406282150500_b10","doi-asserted-by":"crossref","first-page":"430","DOI":"10.1016\/S0168-8278(00)80279-2","article-title":"Rapid detection of genotypes and mutations in the pre-core promoter and the pre-core region of hepatitis B virus genome: correlation with viral persistence and disease severity","volume":"33","author":"Grandjacques","year":"2000","journal-title":"J Hepatol"},{"key":"2022010406282150500_b11","doi-asserted-by":"crossref","first-page":"933","DOI":"10.1084\/jem.180.3.933","article-title":"Cytotoxic T lymphocyte response to a wild type hepatitis B virus epitope in patients chronically infected by variant viruses carrying substitutions within the epitope","volume":"180","author":"Bertoletti","year":"1994","journal-title":"J Exp Med"},{"key":"2022010406282150500_b12","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1038\/369407a0","article-title":"Natural variants of cytotoxic epitopes are T-cell receptor antagonists for antiviral cytotoxic T cells","volume":"369","author":"Bertoletti","year":"1994","journal-title":"Nature"},{"key":"2022010406282150500_b13","doi-asserted-by":"crossref","first-page":"482","DOI":"10.1038\/28860","article-title":"Original antigenic sin impairs cytotoxic T lymphocyte responses to viruses bearing variant epitopes","volume":"394","author":"Klenerman","year":"1998","journal-title":"Nature"},{"key":"2022010406282150500_b14","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1038\/354453a0","article-title":"Human immunodeficiency virus genetic variation that can escape cytotoxic T cell recognition","volume":"354","author":"Phillips","year":"1991","journal-title":"Nature"},{"key":"2022010406282150500_b15","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1128\/JVI.77.1.68-76.2003","article-title":"CD8(+) T cells mediate viral clearance and disease pathogenesis during acute hepatitis B virus infection","volume":"77","author":"Thimme","year":"2003","journal-title":"J Virol"},{"key":"2022010406282150500_b16","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1053\/jhep.2003.50288","article-title":"Week 48 resistance surveillance in two phase 3 clinical studies of adefovir dipivoxil for chronic hepatitis B","volume":"38","author":"Westland","year":"2003","journal-title":"Hepatology"},{"key":"2022010406282150500_b17","doi-asserted-by":"crossref","first-page":"4659","DOI":"10.4049\/jimmunol.150.10.4659","article-title":"HLA A2 restricted cytotoxic T lymphocyte responses to multiple hepatitis B surface antigen epitopes during hepatitis B virus infection","volume":"150","author":"Nayersina","year":"1993","journal-title":"J Immunol"},{"key":"2022010406282150500_b18","doi-asserted-by":"crossref","first-page":"2376","DOI":"10.1128\/jvi.67.4.2376-2380.1993","article-title":"Definition of a minimal optimal cytotoxic T-cell epitope within the hepatitis B virus nucleocapsid protein","volume":"67","author":"Bertoletti","year":"1993","journal-title":"J Virol"},{"key":"2022010406282150500_b19","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1097\/00002371-199907000-00001","article-title":"Induction of cytotoxic T lymphocytes with peptides in vitro: identification of candidate T-cell epitopes in hepatitis B virus X antigen","volume":"22","author":"Chung","year":"1999","journal-title":"J Immunother"},{"key":"2022010406282150500_b20","doi-asserted-by":"crossref","first-page":"3770","DOI":"10.1016\/S0264-410X(02)00297-9","article-title":"HLA-A2 1 restricted peptides from the HBx antigen induce specific CTL responses in vitro and in vivo","volume":"20","author":"Hwang","year":"2002","journal-title":"Vaccine"},{"key":"2022010406282150500_b21","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1038\/334395a0","article-title":"T-cell antigen receptor genes and T-cell recognition","volume":"334","author":"Davis","year":"1988","journal-title":"Nature"},{"key":"2022010406282150500_b22","doi-asserted-by":"crossref","first-page":"2575","DOI":"10.1099\/0022-1317-69-10-2575","article-title":"Typing hepatitis B virus by homology in nucleotide sequence: comparison of surface antigen subtypes","volume":"69","author":"Okamoto","year":"1988","journal-title":"J Gen Virol"},{"key":"2022010406282150500_b23","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1006\/viro.1994.1060","article-title":"Complete genomes, phylogenetic relatedness, and structural proteins of six strains of the hepatitis B virus, four of which represent two new genotypes","volume":"198","author":"Norder","year":"1994","journal-title":"Virology"},{"key":"2022010406282150500_b24","first-page":"67","article-title":"A new genotype of hepatitis B virus: complete genome and phylogenetic relatedness","volume":"81","author":"Stuyver","year":"2000","journal-title":"J Gen Virol"},{"key":"2022010406282150500_b25","doi-asserted-by":"crossref","first-page":"2059","DOI":"10.1099\/0022-1317-83-8-2059","article-title":"Genotype H: a new Amerindian genotype of hepatitis B virus revealed in Central America","volume":"83","author":"Arauz-Ruiz","year":"2002","journal-title":"J Gen Virol"},{"key":"2022010406282150500_b26","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1172\/JCI119559","article-title":"Human histocompatibility leukocyte antigen-binding supermotifs predict broadly cross-reactive cytotoxic T lymphocyte responses in patients with acute hepatitis","volume":"100","author":"Bertoni","year":"1997","journal-title":"J Clin Invest"},{"key":"2022010406282150500_b27","doi-asserted-by":"crossref","first-page":"1527","DOI":"10.1172\/JCI118191","article-title":"Hepatitis B virus (HBV) sequence variation of cytotoxic T lymphocyte epitopes is not common in patients with chronic HBV infection","volume":"96","author":"Rehermann","year":"1995","journal-title":"J Clin Invest"},{"key":"2022010406282150500_b28","doi-asserted-by":"crossref","first-page":"739","DOI":"10.4049\/jimmunol.177.1.739","article-title":"Circulating and liver resident CD4+CD25+ regulatory T cells actively influence the antiviral immune response and disease progression in patients with hepatitis B","volume":"177","author":"Xu","year":"2006","journal-title":"J Immunol"},{"key":"2022010406282150500_b29","doi-asserted-by":"crossref","first-page":"1203","DOI":"10.1093\/intimm\/9.8.1203","article-title":"DNA vaccination with plasmids encoding the intracellular (HBcAg) or secreted (HBeAg) form of the core protein of hepatitis B virus primes T cell responses to two overlapping Kb- and Kd-restricted epitopes","volume":"9","author":"Kuhrober","year":"1997","journal-title":"Int Immunol"},{"key":"2022010406282150500_b30","doi-asserted-by":"crossref","first-page":"2100","DOI":"10.1182\/blood.V99.6.2100","article-title":"ALK as a novel lymphoma-associated tumor antigen: identification of 2 HLA-A2.1-restricted CD8+ T-cell epitopes","volume":"99","author":"Passoni","year":"2002","journal-title":"Blood"},{"key":"2022010406282150500_b31","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1182\/blood-2003-11-4072","article-title":"Identification of an HLA-A*0201-restricted CD8+ T-cell epitope SSp-1 of SARS-CoV spike protein","volume":"104","author":"Wang","year":"2004","journal-title":"Blood"},{"key":"2022010406282150500_b32","first-page":"3735","article-title":"Interleukin 18 transfection enhances antitumor immunity induced by dendritic cell-tumor cell conjugates","volume":"61","author":"Ju","year":"2001","journal-title":"Cancer Res"},{"key":"2022010406282150500_b33","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1126\/science.274.5284.94","article-title":"Phenotypic analysis of antigen-specific T lymphocytes","volume":"274","author":"Altman","year":"1996","journal-title":"Science"},{"key":"2022010406282150500_b34","doi-asserted-by":"crossref","first-page":"1460","DOI":"10.1182\/blood-2002-04-1240","article-title":"Tetramer-assisted identification and characterization of epitopes recognized by HLA A*2402-restricted Epstein\u2013Barr virus-specific CD8+ T cells","volume":"101","author":"Kuzushima","year":"2003","journal-title":"Blood"},{"key":"2022010406282150500_b35","doi-asserted-by":"crossref","first-page":"1499","DOI":"10.1084\/jem.191.9.1499","article-title":"Analysis of successful immune responses in persons infected with hepatitis C virus","volume":"191","author":"Lechner","year":"2000","journal-title":"J Exp Med"},{"key":"2022010406282150500_b36","doi-asserted-by":"crossref","first-page":"1007","DOI":"10.1084\/jem.173.4.1007","article-title":"Analysis of the HLA-restricted influenza-specific cytotoxic T lymphocyte response in transgenic mice carrying a chimeric human\u2013mouse class I major histocompatibility complex","volume":"173","author":"Vitiello","year":"1991","journal-title":"J Exp Med"},{"key":"2022010406282150500_b37","doi-asserted-by":"crossref","first-page":"5096","DOI":"10.4049\/jimmunol.151.9.5096","article-title":"Synthetic peptide in mineral oil adjuvant elicits simian immunodeficiency virus-specific CD8+ cytotoxic T lymphocytes in rhesus monkeys","volume":"151","author":"Yasutomi","year":"1993","journal-title":"J Immunol"},{"key":"2022010406282150500_b38","doi-asserted-by":"crossref","first-page":"2138","DOI":"10.4049\/jimmunol.177.4.2138","article-title":"Screening and identification of severe acute respiratory syndrome-associated coronavirus-specific CTL epitopes","volume":"177","author":"Zhou","year":"2006","journal-title":"J Immunol"},{"key":"2022010406282150500_b39","doi-asserted-by":"crossref","first-page":"195","DOI":"10.4049\/jimmunol.174.1.195","article-title":"Generation of murine CTL by a hepatitis B virus-specific peptide and evaluation of the adjuvant effect of heat shock protein glycoprotein 96 and its terminal fragments","volume":"174","author":"Li","year":"2005","journal-title":"J Immunol"},{"key":"2022010406282150500_b40","doi-asserted-by":"crossref","first-page":"5586","DOI":"10.4049\/jimmunol.153.12.5586","article-title":"The relationship between class I binding affinity and immunogenicity of potential cytotoxic T cell epitopes","volume":"153","author":"Sette","year":"1994","journal-title":"J Immunol"},{"key":"2022010406282150500_b41","first-page":"30","article-title":"An improved method for the detection of peptide-induced upregulation of HLA-A2 molecules on TAP-deficient T2 cells","volume":"13","author":"Regner","year":"1996","journal-title":"Exp Clin Immunogenet"},{"key":"2022010406282150500_b42","doi-asserted-by":"crossref","first-page":"1872","DOI":"10.1182\/blood.V98.6.1872","article-title":"Efficient identification of HLA-A*2402-restricted cytomegalovirus-specific CD8(+) T-cell epitopes by a computer algorithm and an enzyme-linked immunospot assay","volume":"98","author":"Kuzushima","year":"2001","journal-title":"Blood"},{"key":"2022010406282150500_b43","doi-asserted-by":"crossref","first-page":"1022","DOI":"10.1002\/hep.510250438","article-title":"Predominant T-helper 1 cytokine profile of hepatitis B virus nucleocapsid-specific T cells in acute self-limited hepatitis B","volume":"25","author":"Penna","year":"1997","journal-title":"Hepatology"},{"key":"2022010406282150500_b44","doi-asserted-by":"crossref","first-page":"1565","DOI":"10.1084\/jem.174.6.1565","article-title":"Cytotoxic T lymphocytes recognize an HLA-A2-restricted epitope within the hepatitis B virus nucleocapsid antigen","volume":"174","author":"Penna","year":"1991","journal-title":"J Exp Med"},{"key":"2022010406282150500_b45","doi-asserted-by":"crossref","first-page":"1027","DOI":"10.1002\/hep.510260435","article-title":"Molecular features of the hepatitis B virus nucleocapsid T-cell epitope 18\u201327: interaction with HLA and T-cell receptor","volume":"26","author":"Bertoletti","year":"1997","journal-title":"Hepatology"},{"key":"2022010406282150500_b46","doi-asserted-by":"crossref","first-page":"693","DOI":"10.1016\/0092-8674(93)90490-H","article-title":"The antigenic identity of peptide\u2013MHC complexes: a comparison of the conformations of five viral peptides presented by HLA-A2","volume":"75","author":"Madden","year":"1993","journal-title":"Cell"},{"key":"2022010406282150500_b47","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1016\/S0952-7915(98)80110-6","article-title":"HLA\u2013peptide tetrameric complexes","volume":"10","author":"Ogg","year":"1998","journal-title":"Curr Opin Immunol"},{"key":"2022010406282150500_b48","doi-asserted-by":"crossref","first-page":"3067","DOI":"10.1002\/1521-4141(200011)30:11<3067::AID-IMMU3067>3.0.CO;2-L","article-title":"T cell receptor usage of virus-specific CD8 cells and recognition of viral mutations during acute and persistent hepatitis B virus infection","volume":"30","author":"Maini","year":"2000","journal-title":"Eur J Immunol"},{"key":"2022010406282150500_b49","doi-asserted-by":"crossref","first-page":"629","DOI":"10.1038\/346629a0","article-title":"Viral escape by selection of cytotoxic T cell-resistant virus variants in vivo","volume":"346","author":"Pircher","year":"1990","journal-title":"Nature"},{"key":"2022010406282150500_b50","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1016\/S1074-7613(00)80546-4","article-title":"Two human T cell receptors bind in a similar diagonal mode to the HLA-A2\/Tax peptide complex using different TCR amino acids","volume":"8","author":"Ding","year":"1998","journal-title":"Immunity"},{"key":"2022010406282150500_b51","doi-asserted-by":"crossref","first-page":"4003","DOI":"10.4049\/jimmunol.176.7.4003","article-title":"Distinct, cross-reactive epitope specificities of CD8 T cell responses are induced by natural hepatitis B surface antigen variants of different hepatitis B virus genotypes","volume":"176","author":"Riedl","year":"2006","journal-title":"J Immunol"}],"container-title":["Clinical and Experimental Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fj.1365-2249.2007.03570.x","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fj.1365-2249.2007.03570.x","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/academic.oup.com\/cei\/article-pdf\/151\/3\/441\/42045690\/j.1365-2249.2007.03570.x.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/cei\/article-pdf\/151\/3\/441\/42045690\/j.1365-2249.2007.03570.x.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,6,2]],"date-time":"2023-06-02T10:41:08Z","timestamp":1685702468000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/cei\/article\/151\/3\/441\/6494732"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2008,1,24]]},"references-count":51,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2008,1,24]]},"published-print":{"date-parts":[[2008,1,24]]}},"URL":"https:\/\/doi.org\/10.1111\/j.1365-2249.2007.03570.x","relation":{},"ISSN":["0009-9104","1365-2249"],"issn-type":[{"value":"0009-9104","type":"print"},{"value":"1365-2249","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2008,3]]},"published":{"date-parts":[[2008,1,24]]}}}