T cell receptor Vbeta chain restriction and preferred CDR3 motifs of liver-kidney microsomal antigen (LKM-1)-reactive T cells from autoimmune hepatitis patients.
OBJECTIVE
The liver-kidney-microsomal antigen (LKM-1) has been recognized as a major CD4+ T cell antigen in autoimmune hepatitis (AIH). The aim of this study was to characterize the antigen recognition sites of the variable T cell receptor beta-chain (TCRBV) of T cells specific to LKM-1.


METHODS
By repeated stimulation of T cells with a recombinant LKM-1 antigen or an LKM-derived peptide followed by limited dilution, we generated T cell clones. Usage of TCRBV was analyzed by RT-PCR and CDR3 antigen recognition sites were sequenced.


RESULTS
The 18 LKM-1 specific T cell clones isolated from six AIH patients preferentially expressed the TCR elements BV9, BV5S2+S3, BV6, and BV13S1. Four BV9+ T cell clones rearranged the joining element JB1S3 within their CDR3 regions. JB2S3 was detected in another four clones together with BV5S2+S3 or BV13S1. A conserved sequence motif, Q(N)G(X)N, was seen in the diversity regions of five clones (36%). In order to identify T cells expressing the preferred TCRBV molecules in situ, immunohistologic examination of liver biopsies was performed. In AIH patients an accumulation of T cells expressing TCRBV 13S1, BV8 and BV5S3 was observed.


CONCLUSIONS
Our data define TCRBV restriction and preferred CDR3 features of LKM-1 specific T cells. The in situ localization of T cells expressing these restricted TCR molecules may suggest a pathogenic relevance of LKM-1 specific cellular immune responses.
Arenz
M
M
1st Department of Internal Medicine, Johannes Gutenberg-University, Mainz, Germany.
Pingel
S
S
Schirmacher
P
P
Meyer zum Büschenfelde
K H
KH
Löhr
H F
HF
D000293:Adolescent; D000328:Adult; D000368:Aged; D001323:Autoantibodies / Q000235:genetics / Q000276:immunology*; D002999:Clone Cells; D004247:DNA / Q000032:analysis; D005260:Female; D019693:Hepatitis, Autoimmune / Q000276:immunology* / Q000473:pathology; D006521:Hepatitis, Chronic / Q000276:immunology / Q000473:pathology; D006801:Humans; D007124:Immunoenzyme Techniques; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology*; D011994:Recombinant Proteins; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000276:immunology*
D001323:Autoantibodies; D016693:Receptors, Antigen, T-Cell, alpha-beta; D011994:Recombinant Proteins; C060729:anti-liver kidney microsome antibody; D004247:DNA