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

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 αβ T cell populations in the livers of patients with PBC by size spectratyping and sequencing of the T cell receptor (TCR) Vβ transcripts. TCR Vβ 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 Vβ4 clones sharing the Gly (G)-G motif in the CDR3 nDn regions and a Vβ4-Jβ2.7 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 Vβ17 with Jβ2.1 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 Vβ CDR3. We strongly suggest that these clonally expanded T cells might be involved in the immunopathogenesis of PBC.