Identification and precursor frequency analysis of a common T cell epitope motif in mitochondrial autoantigens in primary biliary cirrhosis

Shinji Shimoda, Judith A Van de Water, Aftab Ansari, Minoru Nakamura, Hiromi Ishibashi, Ross L. Coppel, Jack Lake, Emmet B. Keeffe, Thomas E. Roche, M. Eric Gershwin

Research output: Contribution to journalArticle

210 Scopus citations

Abstract

The immunodominant antimitochondrial antibody response in patients with primary biliary cirrhosis (PBC) is directed against the E2 component of the pyruvate dehydrogenase complex (PDC-E2). Based on our earlier observations regarding peripheral blood mononuclear cell (PBMC) T cell epitopes, we reasoned that a comparative analysis of the precursor frequencies of PDC-E2 163-176-specific T cells isolated from PBMC, regional hepatic lymph nodes, and from the liver of PBC patients would provide insight regarding the role oft cells in PBC. Results showed a disease-specific 100-150-fold increase in the precursor frequency of PDC-E2 163-176-specific T cells in the hilar lymph nodes and liver when compared with PBMC from PBC patients. Interestingly, autoreactive T cells and autoantibodies from PBC patients both recognize the same dominant epitope. In addition, we demonstrated cross-reactivity of PDC- E2 peptide 163-176-specific T cell clones with PDC-E2 peptide 3649 and OGDC- E2 peptide 100-113 thereby identifying a common T cell epitope 'motif' ExETDK. The peptide 163176-specific T cell clones also reacted with purified native PDC-E2, suggesting that this epitope is not a cryptic determinant. These data provide evidence for a major role for PDC-E2 peptide 163-176 and/or peptides bearing a similar motif in the pathogenesis of PBC.

Original languageEnglish (US)
Pages (from-to)1831-1840
Number of pages10
JournalJournal of Clinical Investigation
Volume102
Issue number10
StatePublished - Nov 15 1998

Keywords

  • Autoreactive T cells
  • Epitopes
  • Liver
  • Primary biliary cirrhosis
  • Pyruvate dehydrogenase

ASJC Scopus subject areas

  • Medicine(all)

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