We propose to clone and sequence most of the estimated 60 V Beta gene segments of the human T-cell receptor. Representative members of the V Alpha gene segment subfamily will also be cloned and sequenced. We plan to map the chromosomal location of these V gene segments using pulsse gradient gel electrophoresis techniques. We will construct nucleic acid probes specific for each of these V gene segments that should allow us to divide all human T cells into one of 60 categories (corresponding to the 60 V Beta segments). We will also attempt to raise specific antibodies against some of these V segments. We will use these reagents to identify the V Beta (and V Alpha) gene segments employed in human T-cell malignancies and in autoimmune diseases presumably mediated by T cells such as rheumatoid arthritis and multiple sclerosis. We are interested in whether these diseases are mono- or pauciclonal and, if so, in the potential diagnostic and therapeutic potential of the antibody reagents. We also plan to chemically synthesize the T4 homology unit and determine whether it binds to class II MHC molecules.
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