{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T12:59:52Z","timestamp":1788872392112,"version":"build-2803163510"},"reference-count":38,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"5","license":[{"start":{"date-parts":[[2002,11,1]],"date-time":"2002-11-01T00:00:00Z","timestamp":1036108800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"},{"start":{"date-parts":[[2003,12,30]],"date-time":"2003-12-30T00:00:00Z","timestamp":1072742400000},"content-version":"vor","delay-in-days":424,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["DK39588"],"award-info":[{"award-number":["DK39588"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2002,11]]},"abstract":"<jats:sec>\n                    <jats:title\/>\n                    <jats:p>Growing evidence has implicated the involvement of autoreactive T lymphocytes in the pathogenesis of primary biliary cirrhosis (PBC). We have recently taken advantage of motif prediction analysis of HLA-A*0201 and identified the first major histocompatibility complex (MHC) class I restricted epitope, amino acids 159 to 167 on E2 components of pyruvate dehydrogenase complexes (PDC-E2), the major mitochondrial antigens in PBC. The mechanisms involved in the selection of epitope peptide(s) that comprise the PDC-E2-specific autoreactive cytotoxic T lymphocytes (CTLs) are unknown and likely involve other epitopes on PDC-E2 restricted by MHC class I molecules. To address this issue, a comprehensive mapping of the CTL epitope repertoire on the PDC-E2 molecule that binds HLA-A*0201 was performed to provide further clues regarding the role of CTLs. We used the T2 cell line to screen 79 overlapping 15mer peptides, spanning the entire PDC-E2 molecule. Six of the 79 peptides exhibited significantly higher binding activity to HLA-A*0201 than the other 15mer peptides. Two of these 6 peptides induced CTL lines from patients with PBC. Fine mapping with N-terminus or C-terminus truncated peptides identified 10mer peptide, PDC-E2 amino acids 165 to 174, which is a novel CD8 epitope restricted by HLA-A*0201. In conclusion, using a combination of the 15mer peptide library screening with the T2 binding assay and also the induction of CTL lines with candidate peptides, we have defined a novel HLA-A*0201-restricted epitope PDC-E2 165 to 174 in patients with PBC. These data will become important in the development of altered peptide ligands to modulate disease activity.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1053\/jhep.2002.36161","type":"journal-article","created":{"date-parts":[[2003,3,25]],"date-time":"2003-03-25T21:15:53Z","timestamp":1048626953000},"page":"1125-1134","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":43,"title":["Comprehensive mapping of HLA-A*0201-restricted CD8 T-cell epitopes on PDC-E2 in primary biliary cirrhosis"],"prefix":"10.1097","volume":"36","author":[{"given":"Shuji","family":"Matsumura","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroto","family":"Kita","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao-Song","family":"He","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aftab A.","family":"Ansari","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhe-Xiong","family":"Lian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Judy","family":"van de Water","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuhide","family":"Yamamoto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takao","family":"Tsuji","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ross L.","family":"Coppel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marshall","family":"Kaplan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric M.","family":"Gershwin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"10.1053\/jhep.2002.36161-BIB1|cit1","doi-asserted-by":"crossref","first-page":"669","DOI":"10.1084\/jem.194.5.669","article-title":"A pathogenic role for myelin-specific CD8(+) T cells in a model for multiple sclerosis","volume":"194","author":"Huseby","year":"2001","journal-title":"J Exp Med"},{"key":"10.1053\/jhep.2002.36161-BIB2|cit2","doi-asserted-by":"crossref","first-page":"7579","DOI":"10.4049\/jimmunol.166.12.7579","article-title":"Myelin antigen-specific CD8+ T cells are encephalitogenic and produce severe disease in C57BL\/6 mice","volume":"166","author":"Sun","year":"2001","journal-title":"J Immunol"},{"key":"10.1053\/jhep.2002.36161-BIB3|cit3","doi-asserted-by":"crossref","first-page":"1026","DOI":"10.1038\/12465","article-title":"Identification of an MHC class I-restricted autoantigen in type 1 diabetes by screening an organ-specific cDNA library","volume":"5","author":"Wong","year":"1999","journal-title":"Nat Med"},{"key":"10.1053\/jhep.2002.36161-BIB4|cit4","doi-asserted-by":"crossref","first-page":"1923","DOI":"10.1084\/jem.181.5.1923","article-title":"Cytotoxic T cells specific for glutamic acid decarboxylase in autoimmune diabetes","volume":"181","author":"Panina-Bordignon","year":"1995","journal-title":"J Exp Med"},{"key":"10.1053\/jhep.2002.36161-BIB5|cit5","doi-asserted-by":"crossref","first-page":"10859","DOI":"10.1073\/pnas.91.23.10859","article-title":"Autoreactive CD8+ T-cell responses to human myelin protein-derived peptides","volume":"91","author":"Tsuchida","year":"1994","journal-title":"Proc Natl Acad Sci U S A"},{"key":"10.1053\/jhep.2002.36161-BIB6|cit6","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1016\/S0165-5728(96)00105-1","article-title":"A study of human T-cell lines generated from multiple sclerosis patients and controls by stimulation with peptides of myelin basic protein","volume":"70","author":"Pender","year":"1996","journal-title":"J Neuroimmunol"},{"key":"10.1053\/jhep.2002.36161-BIB7|cit7","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1053\/gast.2001.21187","article-title":"H(+),K(+)-atpase (proton pump) is the target autoantigen of Th1-type cytotoxic T cells in autoimmune gastritis","volume":"120","author":"D'Elios","year":"2001","journal-title":"Gastroenterology"},{"key":"10.1053\/jhep.2002.36161-BIB8|cit8","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1172\/JCI9295","article-title":"CD8(+) T-cell autoreactivity to an HLA-B27-restricted self-epitope correlates with ankylosing spondylitis","volume":"106","author":"Fiorillo","year":"2000","journal-title":"J Clin Invest"},{"key":"10.1053\/jhep.2002.36161-BIB9|cit9","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1084\/jem.20010956","article-title":"Identification of HLA-A2-restricted CD8(+). 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