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

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 alpha beta T cell populations in the livers of patients with PBC by size spectratyping and sequencing of the T cell receptor (TCR) vp transcripts. TCR V beta 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 V beta 4 clones sharing the Gly (G)-G motif in the CDR3 non regions and a V beta 4-J beta 2.7 combination in three patients bearing HLA-DR2 and -DQ1. G-Leu (L)Ala (A) or G-L motifs were also seen in the non regions of V beta 17 with J beta 2.1 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 V beta CDR3. We strongly suggest that these clonally expanded T cells might be involved in the immunopathogenesis of PBC. Human Immunology 61: 675-683 (2000). (C) American Society for Histocompatibility and Immunogenetics, 2000. Published by Elsevier Science Inc.