{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T07:10:07Z","timestamp":1791011407667,"version":"4.1.0"},"reference-count":54,"publisher":"Rockefeller University Press","issue":"1","content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2002,1,7]]},"abstract":"<jats:p>Primary biliary cirrhosis (PBC) is characterized by an intense biliary inflammatory CD4+ and CD8+ T cell response. Very limited information on autoantigen-specific cytotoxic T lymphocyte (CTL) responses is available compared with autoreactive CD4+ T cell responses. Using peripheral blood mononuclear cells (PBMCs) from PBC, we identified an HLA-A2\u2013restricted CTL epitope of the E2 component of pyruvate dehydrogenase (PDC-E2), the immunodominant mitochondrial autoantigen. This peptide, amino acids 159\u2013167 of PDC-E2, induces specific MHC class I\u2013restricted CD8+ CTL lines from 10\/12 HLA-A2+ PBC patients, but not controls, after in vitro stimulation with antigen-pulsed dendritic cells (DCs). PDC-E2\u2013specific CTLs could also be generated by pulsing DCs with full-length recombinant PDC-E2 protein. Furthermore, using soluble PDC-E2 complexed with either PDC-E2\u2013specific human monoclonal antibody or affinity-purified autoantibodies against PDC-E2, the generation of PDC-E2\u2013specific CTLs, occurred at 100-fold and 10-fold less concentration, respectively, compared with soluble antigen alone. Collectively, these data demonstrate that autoantibody, helper, and CTL epitopes all contain a shared peptide sequence. The finding that autoantigen\u2013immune complexes can not only cross-present but also that presentation of the autoantigen is of a higher relative efficiency, for the first time defines a unique role for autoantibodies in the pathogenesis of an autoimmune disease.<\/jats:p>","DOI":"10.1084\/jem.20010956","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T16:48:54Z","timestamp":1027702134000},"page":"113-123","update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":240,"title":["Identification of HLA-A2\u2013restricted CD8+ Cytotoxic T Cell Responses in Primary Biliary Cirrhosis"],"prefix":"10.1084","volume":"195","author":[{"given":"Hiroto","family":"Kita","sequence":"first","affiliation":[{"name":"1Division of Rheumatology, Allergy and Clinical Immunology, University of California at Davis School of Medicine, Davis, CA 95616"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhe-Xiong","family":"Lian","sequence":"additional","affiliation":[{"name":"1Division of Rheumatology, Allergy and Clinical Immunology, University of California at Davis School of Medicine, Davis, CA 95616"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Judy","family":"Van de Water","sequence":"additional","affiliation":[{"name":"1Division of Rheumatology, Allergy and Clinical Immunology, University of California at Davis School of Medicine, Davis, CA 95616"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao-Song","family":"He","sequence":"additional","affiliation":[{"name":"1Division of Rheumatology, Allergy and Clinical Immunology, University of California at Davis School of Medicine, Davis, CA 95616"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuji","family":"Matsumura","sequence":"additional","affiliation":[{"name":"1Division of Rheumatology, Allergy and Clinical Immunology, University of California at Davis School of Medicine, Davis, CA 95616"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marshall","family":"Kaplan","sequence":"additional","affiliation":[{"name":"2Department of Gastroenterology, Tufts University School of Medicine, Boston, MA 02111"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Velimir","family":"Luketic","sequence":"additional","affiliation":[{"name":"3Hepatology Section, Medical College of Virginia Commonwealth University, Richmond, VA 23298"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ross L.","family":"Coppel","sequence":"additional","affiliation":[{"name":"4Department of Microbiology, Monash University, Victoria, Clayton, 3168, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aftab A.","family":"Ansari","sequence":"additional","affiliation":[{"name":"5Department of Pathology, Emory University School of Medicine, Atlanta, GA 30322"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. 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