Primary biliary cirrhosis is an enigmatic autoimmune disease that predominantly affects women. The serologic signatures of PBC are high titer antimitochondrial antibodies that are directed at the inner lipoyl domains of the 2-oxo-dehydrogenase enzymes, particularly PDC-E2. Of note, is that the antibody response and the CD4 and CD8 response, are all directed at a similar epitope, the inner lipoyl domain. This unique immunologic response suggests that modification of the inner lipoyl domain is associated with the immunogenetic basis of disease.