Individual and common antigen-recognition sites of liver-derived T cells in patients with autoimmune hepatitis

Scand J Immunol. 2003 Apr;57(4):384-90. doi: 10.1046/j.1365-3083.2003.01236.x.

Abstract

Autoimmune hepatitis (AIH) is characterized by dense T-cell infiltrations in the liver tissue, but little is known how T cells influence the pathogenesis. To address this question, the distribution of T-cell receptor variable beta-chain (TCR Vbeta) transcripts of peripheral blood and liver-infiltrating T cells from previously untreated patients with newly diagnosed acute exacerbated AIH was investigated. Furthermore, the lengths and sequences of complementary-determining region 3 (CDR3) were studied. Reverse transcriptase-polymerase chain reaction (RT-PCR) analysis and CDR3 spectratyping revealed multiple clonal expansions of liver-infiltrating T cells but not peripheral T cells within various TCR Vbeta families. Further analysis of overexpressed TCR Vbeta transcripts using TCR beta-chain-joining element (TCR Jbeta)-specific primers in a nested PCR showed characteristic Vbeta/Jbeta combinations. Subsequent sequencing of CDR3 regions from PCR products confirmed the clonality of T-cell expansions and the usage of common and individual CDR3 motifs. In conclusion, the clonality of expanded T cells within the liver tissue during early clinical manifestation of untreated AIH indicated that autoantigen-specific T cells accumulate at the inflammation site. Individual and common CDR3 motifs argued for predominant epitopes that were recognized by liver-infiltrating T cells in AIH patients.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Amino Acid Sequence
  • Base Sequence
  • Biopsy
  • Clone Cells / immunology
  • Complementarity Determining Regions / biosynthesis
  • Complementarity Determining Regions / genetics
  • Complementarity Determining Regions / immunology
  • Epitopes, T-Lymphocyte / immunology*
  • Female
  • Gene Expression Regulation
  • Hepatitis, Autoimmune / immunology*
  • Hepatitis, Autoimmune / metabolism
  • Humans
  • Male
  • Middle Aged
  • Molecular Sequence Data
  • RNA, Messenger / biosynthesis
  • RNA, Messenger / genetics
  • Receptors, Antigen, T-Cell / biosynthesis
  • Receptors, Antigen, T-Cell / genetics
  • Receptors, Antigen, T-Cell / immunology*
  • Reverse Transcriptase Polymerase Chain Reaction
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / metabolism

Substances

  • Complementarity Determining Regions
  • Epitopes, T-Lymphocyte
  • RNA, Messenger
  • Receptors, Antigen, T-Cell