T-cells specifically recognize their target antigens because they have antigen receptors on their surfaces. Two antigen receptors have been defined. Each of these receptors is though to consist of two immunoglobulin-like polypeptides (alpha and beta or delta and gamma) and they are designated the alpha-beta and delta- gamma receptors respectively. A central concept in our understanding of the interaction between normal T-cells and their target antigens is that the alpha-beta receptor recognizes a foreign antigen in the context of a polymorphic MHC antigen. However, T-cells bearing the delta-gamma receptor appear to be able to recognize target cells in an MHC non-restricted fashion. That is, the delta-gamma receptor does not appear to recognized it antigen in the context of a particular MHC molecule. Eventually we would like to understand how these receptors react with antigens. Furthermore, the delta chain gene rearranges early during the development of a particular T-cell. We propose that expression of a functional delta-gamma chain prevents further T-cell maturation. We propose here to characterize the genes encoding the delta chain and to reconstitute both alpha-beta and delta-gamma receptors in both transformed T-cells and transgenic mice and to use these new reagents to address these issues. Specifically we propose to: 1) clone a cDNA encoding the delta chain of the delta-gamma receptor. 2) Characterize the genes encoding this chain. 3) Clone and express genes encoding alpha and beta chains from receptors with known function. 4) Make transgenic mice that express the clone delta, alpha, and beta chain genes. 5) Determine the effect of the expressed transgene on the development of the T-cell repertoire in these mice. 6) To make transgenic mice that express functional T-cell receptors and to examine the effect of these receptors on the development of the T-cell repertoire.
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