Individual and Common Antigen‐Recognition Sites of Liver‐Derived T Cells in Patients with Autoimmune Hepatitis

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 β‐chain (TCR Vβ) 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 Vβ families. Further analysis of overexpressed TCR Vβ transcripts using TCR β‐chain‐joining element (TCR Jβ)‐specific primers in a nested PCR showed characteristic Vβ/Jβ 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.