title: Identification and precursor frequency analysis of a common T cell epitope motif in mitochondrial autoantigens in primary biliary cirrhosis.
abstract: The immunodominant antimitochondrial antibody response in patients with primary biliary cirrhosis (PBC) is directed against the E2 component of the pyruvate dehydrogenase complex (PDC-E2). Based on our earlier observations regarding peripheral blood mononuclear cell (PBMC) T cell epitopes, we reasoned that a comparative analysis of the precursor frequencies of PDC-E2 163-176-specific T cells isolated from PBMC, regional hepatic lymph nodes, and from the liver of PBC patients would provide insight regarding the role of T cells in PBC. Results showed a disease-specific 100-150-fold increase in the precursor frequency of PDC-E2 163-176-specific T cells in the hilar lymph nodes and liver when compared with PBMC from PBC patients. Interestingly, autoreactive T cells and autoantibodies from PBC patients both recognize the same dominant epitope. In addition, we demonstrated cross-reactivity of PDC-E2 peptide 163-176-specific T cell clones with PDC-E2 peptide 36-49 and OGDC-E2 peptide 100-113 thereby identifying a common T cell epitope "motif" ExETDK. The peptide 163-176-specific T cell clones also reacted with purified native PDC-E2, suggesting that this epitope is not a cryptic determinant. These data provide evidence for a major role for PDC-E2 peptide 163-176 and/or peptides bearing a similar motif in the pathogenesis of PBC.
authors.affiliation: Division of Rheumatology, Allergy and Clinical Immunology, School of Medicine, University of California, Davis, California 95616, USA.
authors.forename: S
authors.initials: S
authors.lastname: Shimoda
authors.forename: J
authors.initials: J
authors.lastname: Van de Water
authors.forename: A
authors.initials: A
authors.lastname: Ansari
authors.forename: M
authors.initials: M
authors.lastname: Nakamura
authors.forename: H
authors.initials: H
authors.lastname: Ishibashi
authors.forename: R L
authors.initials: RL
authors.lastname: Coppel
authors.forename: J
authors.initials: J
authors.lastname: Lake
authors.forename: E B
authors.initials: EB
authors.lastname: Keeffe
authors.forename: T E
authors.initials: TE
authors.lastname: Roche
authors.forename: M E
authors.initials: ME
authors.lastname: Gershwin
mesh_terms: D000328:Adult; D000368:Aged; D001324:Autoantigens / Q000276:immunology*; D002455:Cell Division; D003429:Cross Reactions; D051047:Dihydrolipoyllysine-Residue Acetyltransferase; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D005260:Female; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000166:cytology; D008099:Liver / Q000276:immunology; D008105:Liver Cirrhosis, Biliary / Q000276:immunology*; D008198:Lymph Nodes / Q000276:immunology; D008875:Middle Aged; D008928:Mitochondria / Q000276:immunology*; D010455:Peptides / Q000276:immunology; D011768:Pyruvate Dehydrogenase Complex / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D001324:Autoantigens; D018984:Epitopes, T-Lymphocyte; D010455:Peptides; D011768:Pyruvate Dehydrogenase Complex; D051047:Dihydrolipoyllysine-Residue Acetyltransferase