The analysis of epitope and immunological response of primary biliary cirrhosis

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The pyruvate dehydrogenase E2 component (PDC-E2) is a major antigen for the anti-mitochondria antibody that is a specific autoantibody associated with primary biliary cirrhosis. We have clarified that the major T cell epitope is PDC-E2 163-176 (163 GDLLAEIETDKATI 176), the important site of T cell recognition is 170E, 172D and 173K (ExDK sequence), and the some of human PDC-E2 reactive T cell clones (hPDC-TCC) cross-react with the E-coli PDC-E2 antigen.(Year 1999) The All hPDC-TCC restricted by HLA-DR53 were Th1 type helper T cell, and they reacted not only with the E-coli derived peptide which resembled the molecular mimicry for human PDC-E2 but also the other bacteria derived peptides.(Year 2000) The hPDC-TCC was classified into two groups according to the reactive pattern for the foreign antigen and the autoantigens. The one was the clones that reacted only with the autoantigen of human mitochondria derived proteins, and the other was the clones that reacted not only with the autoantigens but also with the many bacteria derived peptide contained the ExDK motif in the sequence.(Year 2001) Some of the hPDC-TCC cross-reacted with the nuclear antigens, and the clones specific for E-coli OGDC-E2 34-47 also cross-reacted with the human mitochondria autoantigens.We have clarified the existence of cross reactivity of T cell between autoantigens and foreign antigens, and suggested the possibility of molecular mimicry regarding the break of tolerance for the autoantigens.