REGULATION OF RECEPTORS ON T-LYMPHOCYTES

细胞分化期间发生的变化通常涉及 特定基因的激活和抑制。 B和T的共同起源 淋巴细胞表明，在转录重叠的可能性， 调节他们的基因，特别是那些表达后不久， 两种血统的分歧。 这一观点得到了以下观察结果的支持： 免疫球蛋白μ重链基因在某些T细胞中是活跃的 而后来激活的κ轻链基因则没有。 因此，比较早期B和T细胞的转录调控， 基因（以及控制它们的因素）可能会提供关于基因的见解。 信号启动淋巴细胞。 T细胞受体（TCR）β链基因和白细胞介素-2受体 α链基因（IL-2 R α）在T细胞增殖过程的早期表达， 细胞个体发育 本提案中概述的实验旨在确定 顺式作用序列元件（通过转染测定和分析， 转基因小鼠）和相应的反式作用因子， TCR基因的发育正确激活。 这将允许 未来对这些因素本身的调节研究，大概是在 对环境线索的反应。 IL-2 R α在T细胞活化后可进一步诱导， 这可能也适用于TRC基因。 IL-2 R α基因 诱导依赖于结合可诱导的 NF-κ B因子。 奇怪的是，TCR基因座上也有一个类似的基序， 这表明这两个基因可能受同一个因子调控。 预期转染到B和T细胞系中不仅可以阐明细胞的增殖， 这个网站的功能作用，但也揭示了其他监管电路 阻止这些基因在B细胞中的组成型表达， 是本质上存在的。

Changes that take place during cell differentiation often involve the activation and repression of specific genes. The common origin of B and T lymphocytes suggests the possibility of overlap in the transcriptional regulation of their genes, particularly those expressed soon after divergence of the two lineages. This idea is supported by the observation that the immunoglobulin mu heavy chain gene is active in some T cells whereas the later activated kappa light chain gene is not. Thus, comparison of the transcriptional regulation of early B and T cell genes (and the factors that control them) may to provide insights into the signals initiating lymphocyte. The T cell receptor (TCR) beta chain gene and the interleukin-2 receptor alpha chain gene (IL-2Ralpha) are both expressed early in the course of T cell ontogeny. Experiments outlined in this proposal seek to identify the cis-acting sequence elements (by transfection assays and analysis of transgenic mice) and the corresponding trans-acting factors that specify the developmentally correct activation of the TCR genes. This will allow future studies on the regulation of the factors themselves, presumably in response to environmental cues. IL-2Ralpha is further inducible upon T cell activation and recent reports suggest that this might be true of the TRC genes as well. IL-2Ralpha gene induction is dependent upon a sequence motif that binds the inducible factor NF-KB. Curiously, a similar motif is located in the TCR locus as well, suggesting that both genes may be regulated by the same factor. Transfections into B and T cell lines is expected to not only clarify the functional role of this site but to also reveal other regulatory circuits that prevent constitutive expression of these genes in B cells where NR-KB is constituitively present.