Autoantibodies to BCOADC-E2 in patients with primary biliary cirrhosis recognize a conformational epitope

Hepatology. 1995 Aug;22(2):505-13.


Primary biliary cirrhosis (PBC) is an autoimmune disease of liver associated with a unique serologic response to mitochondrial autoantigens. Many of the autoantigens recognized by autoantibodies in PBC are members of the 2-oxo-acid dehydrogenase complex. The two major autoantigens are the E2 component of the pyruvate dehydrogenase complex (PDC-E2) and the E2 component of the branched chain 2-oxo-acid dehydrogenase complex (BCOADC-E2). The autoantibody response to PDC-E2 has been mapped to one immunodominant epitope, which consists of both linear and conformational components. The presence of a single immunodominant epitope in PDC-E2 is unusual when contrasted to the immune response to autoantigens in other human autoimmune diseases. We have mapped the epitope recognized by antimitochondrial autoantibodies (AMA) specific to BCOADC-E2 in patients with PBC by taking advantage of the full-length bovine BCOADC-E2 complementary DNA (cDNA) and a series of expression clones spanning the entire molecule. Reactivity to the various expression clones was studied by immunoblotting, enzyme-linked immunosorbent assay (ELISA), as well as selective absorption of patient sera by expressed protein fragments. Autoantibodies to BCOADC-E2 map within peptides spanning amino acid residues 1 to 227 of the mature protein; our data demonstrate that the epitope is dependent on conformation and includes the lipoic acid binding region. However, only the full-length clone (amino acid residue 1 to 421) is sufficient to remove all detectable BCOADC-E2 reactivity. Moreover, the absence of lipoic acid on the recombinant polypeptides used in this study indicates that antibody binding to BCOADC-E2 is not dependent on the presence of lipoic acid.

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide)
  • Amino Acid Sequence
  • Antibody Specificity
  • Autoantibodies / blood*
  • Autoantigens / chemistry
  • Autoantigens / immunology
  • Binding Sites
  • Enzyme-Linked Immunosorbent Assay
  • Epitopes / chemistry*
  • Epitopes / immunology
  • Humans
  • Immunosorbent Techniques
  • Ketone Oxidoreductases / immunology*
  • Liver Cirrhosis, Biliary / immunology*
  • Molecular Sequence Data
  • Multienzyme Complexes / immunology*
  • Protein Conformation
  • Recombinant Proteins / analysis
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / immunology
  • Sequence Analysis
  • Sequence Homology
  • Thioctic Acid / analysis
  • Thioctic Acid / metabolism


  • Autoantibodies
  • Autoantigens
  • Epitopes
  • Multienzyme Complexes
  • Recombinant Proteins
  • Thioctic Acid
  • Ketone Oxidoreductases
  • 3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide)