Analysis of T cell receptors specific for U1-70kD small nuclear ribonucleoprotein autoantigen: the alpha chain complementarity determining region three is highly conserved among connective tissue disease patients.
The U1-70kD autoantigen is a major target of B cell responses in patients with connective tissue diseases (CTD). T cell responses are important in the pathogenesis of CTD, however little is known about autoantigen-specific T cells in these diseases. We have recently proven that U1-70kD-reactive human T cells exist. To further characterize these autoreactive T cells, U1-70kD-reactive T cell clones have been generated from patients with CTD using either a recombinant fusion protein or synthetic peptides spanning the U1-70kD polypeptide. T cell receptors (TCR) isolated from the U1-70kD-reactive T cell clones were sequenced and the third complementarity-determining region (CDR3) compared to determine if a common motif was present. mAb blocking of antigen-induced proliferation was done to determine the HLA restriction element used in recognition of the U1-70kD autoantigen by T cells. The results presented here indicate that TCRAV CDR3 usage is highly restricted among U1-70kD autoantigen-specific human T cells clones derived from CTD patients with distinctive structural features. Furthermore, the recognition of the U1-70kD autoantigen occurs in the context of HLA-DR.
D000595:Amino Acid Sequence; D001324:Autoantigens / Q000276:immunology*; D002999:Clone Cells; D003198:Computer Simulation; D003240:Connective Tissue Diseases / Q000209:etiology / Q000276:immunology*; D017124:Conserved Sequence; D015329:Gene Rearrangement, T-Lymphocyte; D006684:HLA-DR Antigens / Q000276:immunology; D006801:Humans; D007135:Immunoglobulin Variable Region; D008180:Lupus Erythematosus, Systemic / Q000209:etiology / Q000276:immunology; D008947:Mixed Connective Tissue Disease / Q000209:etiology / Q000276:immunology; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000276:immunology; D016693:Receptors, Antigen, T-Cell, alpha-beta; D017412:Ribonucleoprotein, U1 Small Nuclear / Q000276:immunology*; D017422:Sequence Analysis, DNA; D013601:T-Lymphocytes / Q000276:immunology*