This proposal analyzes the relationship between the T cell receptor alpha/beta molecules and the antigen binding chain of soluble suppressor T cell derived factors. We propose several approaches to establish a relationship between components of the conventional CD3-TcR complex and the antigen specific regulatory factors released by suppressor T cell hybridomas. Data presented in the application demonstrate the use of TcR expression variants' and TcR-alpha transfection to directly address this issue. Additional experiments are proposed to extend these observations and to evaluate if TsF with new antigen specificity can be engineered. Additional studies are aimed at comparing and defining the chains associated with inducer (TsF1) and effector (TsF3) suppressor factors. These studies will test the hypothesis that TsF consists of a heterodimer composed of TcR-alpha plus either of two distinct nonspecific suppressive molecules which may express phospholipase inhibitory activity. Specific experiments involve heterologous transfections and bioassays to determine the relationships between various serological determinants associated with TsF bioactivity. Finally, we propose to biochemically isolate and characterize TsF. The combined aims should provide a better understanding of suppressor T cells and their products. The phenomenon of T cell mediated suppression may play a central role in the homeostatic mechanisms which normally regulate immune responses. Thus, this proposal may have direct application for control of autoimmunity and cancer.
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