EXPRESSION OF T CELL RECEPTOR GAMMA AND DELTA CHAINS

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MHC-restricted, antigen-specific recognition by T cells is mediated by a receptor complex of CD3 associated with the alpha beta heterodimer. The thymus and spleen of mice and man contain a small population of T cells that express an alternative CD3-associated receptor of gamma and delta chains. Little is known of the functional role of the gamma-delta receptor, nor its ontogenic relationship to alpha-beta. Less is known of the complex and apparently ordered events that regulate gamma and delta gene expression. We have recently shown that the major T cell component of the mouse epidermis, Thy1+ dEC cells, express gamma-delta receptors of a restricted repertoire, akin to that of early fetal thymus. Moreover, we have shown that gamma and delta chain RNA synthesis in dEC cells can be modulated by Con A. Using Thyl+dEC as a model system, we propose to extend these observations by (1) Establishing the level at which Con A acts to induce higher levels of delta chain mRNA and lower levels of gamma chain mRNA while simultaneously inducing secretion of IL-2. (2) Determining whether anti-gamma-delta receptor antibodies that also induce secretion of IL-2 from dEC clones induce changes in gamma-delta message, protein and surface expression. (3) Establishing the role of conserved promoter-enhancer associated sequences in tissue-specific transcription and induction of gamma and delta genes. (4) Isolating, characterizing and cloning the genes for proteins that functionally interact with gamma and delta associated regulatory sequences. (5) Characterizing a spontaneous switch from functional gamma-delta to functionally alpha-beta RNA expression in a dEC clone.