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 beta-chain (TCR Vbeta) 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 Vbeta families. Further analysis of overexpressed TCR Vbeta transcripts using TCR beta-chain-joining element (TCR Jbeta)-specific primers in a nested PCR showed characteristic Vbeta/Jbeta 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.
Löhr
H F
HF
Department of Internal Medicine, Johannes-Gutenberg-University Mainz, Langenbeckstrasse 1, 55122 Mainz, Germany. loehr@mail.uni-mainz.de
Pingel
S
S
Weyer
S
S
Fritz
T
T
Galle
P R
PR
D000328:Adult; D000368:Aged; D000595:Amino Acid Sequence; D001483:Base Sequence; D001706:Biopsy; D002999:Clone Cells / Q000276:immunology; D022801:Complementarity Determining Regions / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D005260:Female; D005786:Gene Expression Regulation; D019693:Hepatitis, Autoimmune / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D011948:Receptors, Antigen, T-Cell / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism
D022801:Complementarity Determining Regions; D018984:Epitopes, T-Lymphocyte; D012333:RNA, Messenger; D011948:Receptors, Antigen, T-Cell