REGULATION OF RECEPTORS ON T-LYMPHOCYTES

B和T细胞起源于共同的前体表明可能存在 在基因转录调控上有重叠，特别是那些 在两个谱系分化后不久表达。因素分析 调节早期淋巴基因的表达应该能提供对 导致B和T细胞分化的信号。 TCRβ基因在T细胞个体发育早期表达，可能与 具有免疫球蛋白Mu重链基因调控功能。白介子- 2Rpha基因通过序列元件在T细胞激活时被诱导 与核因子-kB结合位点同源，最初在 免疫球蛋白K轻链基因增强子。当前的目标是 本申请中概述的实验旨在定义(通过转染法和 转基因小鼠分析)适当的 TCR-β和IL-2Rα基因的表达及鉴定 与这些序列相互作用的反式作用因子。这些研究 预计将使我们在探索淋巴发育方面处于有利地位 通过确定在启动或关闭基因方面起关键作用的因素 B细胞和T细胞发育的不同阶段。

Origin of B and T cells from a common precursor suggests that there might be overlap in the transcriptional regulation of genes, particularly those expressed soon after divergence of the 2 lineages. Analysis of factors regulating early lymphoid gene expression should provide insights into the signals leading to B and T cell differentiation. The TCR beta gene is expressed early during T cell ontogeny and may share regulatory features with the immunoglobulin mu heavy chain gene. The IL- 2Ralpha gene is induced upon T cell activation via a sequence element homologous to the NF-kB binding site, originally identified in the immunoglobulin k light chain gene enhancer. The immediate goals of the experiments outlined in this application are to define (by transfection and transgenic mouse analysis) the sequence elements required for appropriate expression of the TCR-beta and IL-2Ralpha genes and subsequently identified the trans-acting factors interacting with these sequences. These studies are expected to place us in a strong position to probe lymphoid development by identifying factors that are critical in turning genes on or off at different stages of B and T cell development.