T cell repertoire in the liver of patients with primary biliary cirrhosis

Hum Immunol. 2000 Jul;61(7):675-83. doi: 10.1016/s0198-8859(00)00129-4.

Abstract

Primary biliary cirrhosis (PBC) is an autoimmune chronic liver disease characterized by the destruction of the bile ducts with an accumulation of lymphocytes. To investigate the roles of T cells accumulating around the bile ducts, we analyzed the clonality of alphabeta T cell populations in the livers of patients with PBC by size spectratyping and sequencing of the T cell receptor (TCR) Vbeta transcripts.TCR Vbeta spectratyping of PBC patients showed several skewed complementarity determining region 3 (CDR3) size patterns suggestive of clonal predominance as well as Gaussian-like patterns suggestive of polyclonal expansion. We observed Vbeta4 clones sharing the Gly (G)-G motif in the CDR3 nDn regions and a Vbeta4-Jbeta2.7 combination in three patients bearing HLA-DR2 and -DQ1. G-Leu (L)-Ala (A) or G-L motifs were also seen in the nDn regions of Vbeta17 with Jbeta2.1 of the two patients having HLA-A26. However, there were no whole CDR3-shared clones in any of the patients. In conclusion, we have observed that T cell clones are heterogeneous in each patient, but that they have some common motifs in the TCR Vbeta CDR3. We strongly suggest that these clonally expanded T cells might be involved in the immunopathogenesis of PBC.

MeSH terms

  • Amino Acid Sequence
  • Female
  • Histocompatibility Testing
  • Humans
  • Liver / cytology*
  • Liver Cirrhosis, Biliary / immunology*
  • Male
  • Middle Aged
  • Molecular Sequence Data
  • Receptors, Antigen, T-Cell, alpha-beta / genetics
  • Receptors, Antigen, T-Cell, alpha-beta / immunology*
  • T-Lymphocytes / cytology
  • T-Lymphocytes / immunology*

Substances

  • Receptors, Antigen, T-Cell, alpha-beta