T-CELL RESPONSES TO NATURAL HUMAN PROTEINS IN PRIMARY BILIARY-CIRRHOSIS

The study of T cell responses to autoantigens in human autoimmunity ha s been hampered by difficulties, firstly in identifying significant au toantigens, and secondly in the purification of authentic human protei ns in sufficient quantities to allow characterization of antigen-speci fic T cell responses. In this study we have purified a human autoantig en, pyruvate dehydrogenase, retaining its enzymatic activity, and char acterized autoreactive T cell responses to it in a human autoimmune di sease, primary biliary cirrhosis. T cell responses to a mixture of the E2 and protein X subunits of human pyruvate dehydrogenase complex are seen in most affected patients, but in only a small minority of norma l and chronic liver disease controls. By contrast, responses to whole pyruvate dehydrogenase complex occur with equal frequency in both grou ps. This suggests that responses to the E2 component/protein X of pyru vate dehydrogenase complex play a role in the pathogenesis of primary biliary cirrhosis. The availability of significant quantities of the h uman autoantigen in primary biliary cirrhosis makes this condition an interesting model in which to study true autoreactive human T cell res ponses.