{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,29]],"date-time":"2025-09-29T20:35:50Z","timestamp":1759178150274,"version":"3.37.3"},"reference-count":44,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"4","license":[{"start":{"date-parts":[[2002,10,1]],"date-time":"2002-10-01T00:00:00Z","timestamp":1033430400000},"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":455,"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":[[2002,10]]},"abstract":"<jats:sec>\n            <jats:title\/>\n            <jats:p>Although the etiology and mechanism of primary biliary cirrhosis (PBC) is unknown, growing evidence suggests a major role for T cells. We have recently identified the first CD8 T-cell epitope, amino acid 159-167 of the E2 component of pyruvate dehydrogenase complexes (PDC-E2). To seek for analogue peptide-antagonizing effector function of CTLs specific for this autoantigen, we examined the effector functions of the PDC-E2-specific CTLs against alanine substituted peptides. Furthermore, because molecular mimicry has been postulated as a possible cause of initiating PBC, we carried out studies aimed at identifying naturally occurring peptides for the 159-167 peptide of PDC-E2 that may serve as agonists. An alanine substitution at position 5 of this epitope significantly reduced peptide-specific effector functions of CTLs. Moreover, this analogue peptide inhibited effector functions of the CTLs to the prototype peptide, including cytotoxicity and IFN-\u03b3 production. We also identified a peptide derived from <jats:italic toggle=\"yes\">Pseudomonas aeruginosa<\/jats:italic>, which showed a higher binding affinity to the HLA-A*0201 than the prototype peptide. This homologous peptide was recognized by CTLs specific for the prototype epitope on PDC-E2. In conclusion, a modification of the immunodominant autoepitope can be utilized to manipulate the CD8 T-cell responses against the autoantigen PDC-E2. Our finding also supports the thesis that molecular mimicry may be implicated in the initiation of the autoreactive CD8 T-cell responses and has implications for the use of such peptides for immunotherapy.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1053\/jhep.2002.35616","type":"journal-article","created":{"date-parts":[[2003,3,26]],"date-time":"2003-03-26T02:15:53Z","timestamp":1048644953000},"page":"918-926","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":22,"title":["Analysis of TCR antagonism and molecular mimicry of an HLA-A*0201-restricted CTL epitope in primary biliary cirrhosis"],"prefix":"10.1097","volume":"36","author":[{"given":"Hiroto","family":"Kita","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shuji","family":"Matsumura","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiao-Song","family":"He","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aftab A.","family":"Ansari","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhe-Xiong","family":"Lian","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Judy","family":"Van de Water","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ross L.","family":"Coppel","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marshall 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