PBC is associated with other autoimmune diseases, both within individuals and among families, reflecting the "clustering" characteristic for autoimmunity [183] . PBC was one of the first conditions in which the presence of autoantibodies in the serum was identified and in which the antigen specificity of this autoreactive response was characterized [5] . It is therefore often referred to as a "model autoimmune disease." The predominant autoreactive antibodies in PBC are AMAs, which, with a high sensitivity and specificity, are virtually diagnostic for PBC when detected in serum. The so far identified targets of AMA are all members of the family of 2-oxo-acid dehydrogenase complexes (2-OADC). This includes the E2 subunits of the pyruvate dehydrogenase complex (PDC-E2), the branched chain 2-oxo-acid dehydrogenase complex (BCOADC-E2), the 2-oxo-glutaric acid dehydrogenase complex (OGDC-E2), and the dihydrolipoamide dehydrogenase binding protein (E3BP) [184] , all localized within the inner mitochondrial matrix, catalyzing oxidative decarboxylation of keto acid substrates. The targeted E2 subunits all have a common N-terminal domain containing single or multiple attachment sites for a lipoic acid cofactor to lysine. Previous studies have demonstrated that the dominant epitopes recognized by AMA are all located within these lipoyl domains of the target antigens [185] [186] [187] [188] . The autoreactive CD4 and CD8 T cells infiltrating the liver in PBC recognize the same PDC-E2 domain (peptides 159-167 and 163-176) [189, 190] , and the same accounts for the dominant autoreactive B cells [191] . CD8 T cells isolated from livers of patients with PBC have been found to exert cytotoxicity against PDC-E2 pulsed autologous cells (peptides 159-167) [192] , supporting the hypothesis of a T cell response contributing to bile duct injury in PBC.