Immunoreactivity of porcine heart dihydrolipoamide acetyl- and succinyl-transferases (PDC-E2, OGDC-E2) with primary biliary cirrhosis sera: characterization of the autoantigenic region and effects of enzymatic delipoylation and relipoylation

Hepatology. 1998 Jun;27(6):1467-74. doi: 10.1002/hep.510270602.


Analysis of the primary structure of the lipoyl domain of the dihydrolipoamide acetyltransferase (PDC-E2) component of the porcine pyruvate dehydrogenase complex (PDC) reveals a high degree of homology with M2 antigen and human PDC-E2. The porcine PDC-E2 and the dihydrolipoamide succinyltransferase (OGDC-E2) component of the porcine 2-oxoglutarate dehydrogenase complex (OGDC) were identified as mitochondrial autoantigen with sera from patients with primary biliary cirrhosis (PBC). Immunodominant regions (autoepitopes) on the porcine-PDC-E2 component have been mapped to two regions around Lys-46 (outer lipoyl domain) and Lys-173 (inner lipoyl domain), which contained covalently bound lipoic acid prosthetic group. When these lipoyl domains were cleaved at Asp-45 or Asp-172 with endoproteinase Asp-N, the autoantigenicities of the two domains completely disappeared; this suggested the requirement of Asp-45 or Asp-172 residues for the immunoreaction with PBC sera. In addition, a single 14-amino acid epitope peptide histidine-substituted at Asp-172 did not exhibit competitive inhibition of autoantigen binding. Fragmentation of lipoyl domain of the porcine PDC-E2 by limited proteolysis and BrCN-cleavage after alkylation resulted in rapid loss of autoantigenicity. Enzymatic delipoylation and relipoylation of the complexed and free PDC-E2 and OGDC-E2 components did not influence immunoreactivity with PBC sera.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Antibody Specificity
  • Autoantibodies / blood
  • Autoantibodies / immunology*
  • Autoantigens / immunology*
  • Dihydrolipoyllysine-Residue Acetyltransferase
  • Humans
  • Immunodominant Epitopes / immunology*
  • Ketoglutarate Dehydrogenase Complex / immunology*
  • Liver Cirrhosis, Biliary / blood
  • Liver Cirrhosis, Biliary / immunology*
  • Molecular Sequence Data
  • Pyruvate Dehydrogenase Complex / immunology*
  • Swine


  • Autoantibodies
  • Autoantigens
  • Immunodominant Epitopes
  • Pyruvate Dehydrogenase Complex
  • Ketoglutarate Dehydrogenase Complex
  • Dihydrolipoyllysine-Residue Acetyltransferase