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 w ith 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 huma n T cells exist. To further characterize these autoreactive T cells, U1-70k D-reactive T cell clones have been generated from patients with CTD using e ither a recombinant fusion protein or synthetic peptides spanning the U1-70 kD 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 o f antigen-induced proliferation was done to determine the HLA restriction e lement used in recognition of the U1-70kD autoantigen by T cells. The resul ts presented here indicate that TCRAV CDR3 usage is highly restricted among U1-70kD autoantigen-specific human T cells clones derived from CTD patient s with distinctive structural features. Furthermore, the recognition of the U1-70kD autoantigen occurs in the context of HLA-DR. Human Immunology 60, 200-208 (1999). (C) American Society for Histocompatibility and Immunogenet ics, 1999. Published by Elsevier Science Inc.