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Individual and Common Antigen‐Recognition Sites of Liver‐Derived T Cells in Patients with Autoimmune Hepatitis
Author(s) -
Löhr H. F.,
Pingel S.,
Weyer S.,
Fritz T.,
Galle P. R.
Publication year - 2003
Publication title -
scandinavian journal of immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.934
H-Index - 88
eISSN - 1365-3083
pISSN - 0300-9475
DOI - 10.1046/j.1365-3083.2003.01236.x
Subject(s) - t cell receptor , autoimmune hepatitis , biology , polymerase chain reaction , epitope , t cell , immunology , antigen , hepatitis , pathogenesis , cd3 , gene , microbiology and biotechnology , immune system , cd8 , genetics
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.