IDENTIFICATION AND PRECURSOR FREQUENCY-ANALYSIS OF A COMMON T-CELL EPITOPE MOTIF IN MITOCHONDRIAL AUTOANTIGENS IN PRIMARY BILIARY-CIRRHOSIS

The immunodominant antimitochondrial antibody response in patients wit h 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 fr equencies of PDC-E2 163-176-specific T cells isolated from PBMC, regio nal hepatic lymph nodes, and from the liver of PBC patients would prov ide insight regarding the role of T cells in PBC. Results showed a dis ease-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 co mpared with PBMC from PBC patients. Interestingly, autoreactive T cell s and autoantibodies from PBC patients both recognize the same dominan t epitope. In addition, we demonstrated cross-reactivity of PDC-E2 pep tide 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 ''moti f'' ExETDK. The peptide 163-176-specific T cell clones also reacted wi th purified native PDC-E2, suggesting that this epitope is not a crypt ic determinant. These data provide evidence for a major role for PDC-E 2 peptide 163-176 and/or peptides bearing a similar moth in the pathog enesis of PBC.