T cell activation is controlled by a highly organized multi-molecular structure at the T cell-antigen presenting cell interface. This structure has recently been termed an """"""""immunological synapse."""""""" In an effort to find novel molecules involved in this synapse, they have identified a family of five previously uncloned cadherin-like lymphocyte transmembrane proteins (the CLASP family). At least one member of the family, murine CLASP-I, is localized at the immunological synapse. The goals of phase I of this research project are to clone and sequence at least three human genes of this family and to determine their tissue expression patterns and chromosomal localization. In addition, molecules that interfere with CLASP function, such as monoclonal antibodies or recombinant soluble CLASP proteins, will be synthesized and their effect on lymphocyte activation tested in vitro. In stage II of the project, the toxicity and efficacy of these potential therapeutics will be evaluated in animal models of organ transplantation and autoimmune disease and if positive results are obtained in clinical trials in humans. Together these studies should further their molecular understanding of the immunological synapse and yield commercially viable products that, by targeting this synapse, allow improved pharmacological regulation of the immune system.
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