REGULATED EXPRESSION OF T CELL GAMMA AND DELTA CHAINS

在第1-4年，我们研究了结构-功能和基因 γ δ TcR的调节。我们特别关注的是V γ 3/V γ 1受体在第一胎波和大多数胎波中表达 成年树突状表皮T细胞。此次更新解决了 选择性γ δ表达来源于 因子介导的有序V（D）J重组的发育程序 影响特异性V γ/V δ启动子转录- 相关序列。测试该模型的实验分为两组 目标。首先，我们希望更好地了解增强子依赖性的规则， 和独立的V γ 3/V δ 1转录。接下来，我们希望利用 这一信息发展直接联系生殖细胞转录 和V（D）J重组。我们认为那个与V星人有关的消音器 序列对于这两个事件的时间安排至关重要。我们试图 设计假设驱动的培养细胞和转基因实验 分离了反式作用因子所起作用的小鼠， 转录本身和染色质状态。

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.