The long-term goal of this project remains a directed investigation of the regulation of T-cell receptor (TCR) gene activity during T cell ontogeny. Specifically, we will focus on parameters influencing recombinase enzyme activity in pre-T cell populations, in transformed pre-T cell lines and in autoimmune gld mice. In order to dissect the mechanisms by which recombinase is regulated, we propose to: 1. Characterize external signals regulating recombinase activity during T cell development by identifying the cytokines and/or cell surface molecules expressed on thymic stromal cells, which induce or suppress recombinase enzyme activity. 2. Examine recombinase regulation in gld autoimmune mice by 1) assessing the extent and nature of the recombinase defect(s) in gld mice by analyzing recombinase activity in cell lines derived from these mice and 2) analyzing the effect of aberrant gld recombinase activity on somatic recombination in vivo.
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