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

• Published in: Scandinavian journal of immunology 2003-04, Vol.57 (4), p.384-390
• Main Authors: Löhr, H. F., Pingel, S., Weyer, S., Fritz, T., Galle, P. R.
• Format: Article
• Language: English
• Subjects: Adult; Aged; Amino Acid Sequence; Base Sequence; Biopsy; Clone Cells - immunology; Complementarity Determining Regions - biosynthesis; Complementarity Determining Regions - genetics; Complementarity Determining Regions - immunology; Epitopes, T-Lymphocyte - immunology; Female; Gene Expression Regulation; Hepatitis, Autoimmune - immunology; Hepatitis, Autoimmune - metabolism; Humans; Male; Middle Aged; Molecular Sequence Data; Receptors, Antigen, T-Cell - biosynthesis; Receptors, Antigen, T-Cell - genetics; Receptors, Antigen, T-Cell - immunology; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - biosynthesis; RNA, Messenger - genetics; T-Lymphocytes - immunology; T-Lymphocytes - metabolism
• ISSN: 0300-9475; 1365-3083
• DOI: 10.1046/j.1365-3083.2003.01236.x

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.