Il2 Receptors--molecular Regulation

人类白细胞介素-2受体正在研究中，以了解正常和肿瘤细胞中T细胞免疫应答的关键成分。T细胞活化后，IL-2和IL-2受体被诱导; T细胞免疫应答的幅度和持续时间由产生的IL-2的量、表达的受体水平和这些事件的时间过程控制。存在IL-2受体的三条链，IL-2 Ra、IL-2 Rb和gc，其中IL-2 Ra和IL-2 Rb在转录水平上受到显著调节。该小组主要关注IL-2诱导的信号类型，特别是STAT蛋白（信号转导和转录激活因子）的激活，以及它们调节IL-2 Ra基因的机制。Stat 5a和Stat 5 b是两种密切相关的蛋白质，具有>90%的氨基酸同一性，由IL-2激活。一个重要的问题是，这些密切相关的蛋白质在它们的作用中是否是多余的或独特的。为了试图澄清这个问题，已经产生了Stat 5a和Stat 5 b转基因小鼠来重建敲除小鼠。发现Stat 5蛋白在调节CD 8 + T细胞稳态中的主要作用。Stat 5a和Stat 5 b是位于头对头方向的相邻基因。目前正在研究这些基因调控的相似性与差异性。IL-2 Ra基因中有两个IL-2应答元件，一个位于5'调控区，另一个位于第一内含子。该第二调节元件，表示为PRRIV，据报道也是TCR应答元件。该元件在人类和小鼠中高度保守，位于第一内含子中。该元件不仅受Stat 5和HMG-I（Y）蛋白的调节，还受NFAT和AP 1位点的调节。内含子元件与上游元件一起控制IL-2 Ra基因的IL-2介导和TCR介导的调节。总之，这些研究大大增强了我们对IL-2 R表达和Stat 5依赖性基因调控基础的理解。

The human interleukin-2 receptor is being studied to understand critical components of the T cell immune response in normal and neoplastic cells. Following T-cell activation, IL-2 and IL-2 receptors are induced; the magnitude and duration of the T-cell immune response is controlled by the amount of IL-2 produced, the levels of receptors expressed, and the time course of these events. Three chains of the IL-2 receptor exist, IL-2Ra, IL-2Rb, and gc, with IL-2Ra and IL-2Rb being significantly regulated at the level of transcription. The group has focused primarily on the types of signals induced by IL-2, particularly the activation of STAT proteins (signal transducers and activators of transcription), and the mechanism by which they regulate the IL-2Ra gene. Stat5a and Stat5b are two closely related proteins with >90% amino acid identity that are activated by IL-2. An important issue is whether these closely related proteins are redundant or distinctive in their actions. To attempt to clarify this issue, Stat5a and Stat5b transgenic mice have been generated to reconstitute the knockout mice. A major role for Stat5 proteins in regulating CD8+ T cell homeostasis was discovered. Stat5a and Stat5b are adjacent genes located in a head-to-head orientation. Aspects of similarities vs. differences in regulation of these genes is being studied. Two IL-2 response elements in the IL-2Ra gene were previously reported, one in the 5' regulatory region and the other in the first intron. This second regulatory element, denoted PRRIV, was reported to be a TCR response element as well. This element is highly conserved in humans and mice and is located in the first intron. This element is regulated not only by Stat5 and HMG-I(Y) proteins but also by NFAT and AP1 sites. Together with the upstream elements, the intronic element controls IL-2-mediated and TCR-mnediated regulation of the IL-2Ra gene. Together, these studies substantially enhance our understanding of the basis of IL-2R expression and Stat5-dependent gene regulation.