Research Abstract

During thymic development, thymocytes undergo a stringent selection process whereby cells expressing an inappropriate T cell receptor (TCR) are triggered to undergo apoptosis. Our recent biochemical analyses have identified a TCR-activated thymic caspase responsible for the apoptosis of thymocytes undergoing negative selection. Given that TCR triggering events require a second signal for efficient deletion of double positive (DP) thymocytes and that caspases are not physically associated with the TCR, we plan to examine the DP thymocytes for caspase-associated death receptor molecules whose expression is TCR-regulated. Elucidation of negative selection mechanisms will contribute to an understanding of the basis of tolerance with the potential health benefit of developing modifiers of this process which will aid in the treatment of autoimmune disease states, or, perhaps, provide a basis for control of immune responses by shaping the TCR repertoire to recognize known tumor antigens.

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