In years 1-4 of this grant we studied both structure-function and gene regulation of gamma delta TcR. Our specific focus was the V gamma 3/V gamma 1 receptor expressed in the first fetal wave and on the majority of adult dendritic epidermal T cells. This renewal addresses the hypothesis that selective gamma delta expression derives from a developmental program for ordered V(D)J recombination mediated by factors that affect transcription from specific V gamma/V delta promoter- associated sequences. Experiments to test this model are grouped into two aims. First, we hope to better understand the rules of enhancer-dependent and independent V gamma 3/V delta 1 transcription. Next, we hope to use this information to develop direct links between germline transcription and V(D)J recombination. We feel that putative V-associated silencer sequences are central to the timing of both events. We have attempted to design hypothesis-driven experiments in cultured cells and transgenic mice that segregate the roles played by transacting factors, transcription per se, and chromatin state.
