Antigen receptor inputs: linking structural, molecular, and cellular responses

该计划的首要目标是了解调节细胞的分子机制 激活。通过对抗原的特异性识别激活淋巴细胞的姿势是狭义平衡的 收益和风险并存，因此受到严格监管。我们知道一些信号用来调制或 终止激活，而其他信号导致细胞无反应或死亡。分子机制 不同结果的监管过程背后是未知的，而且在很大程度上是未知的。 该方案由五个高度互动的项目组成，涉及来自五个不同国家的六名调查人员 大学的各系。这些调查人员带来了创新的技术和精辟的想法 淋巴细胞活化及其调控问题。这五个项目涵盖了一系列刺激、线索和 从最初的事件中导致T细胞激活或无反应的各种状态的结果 抗原识别对转录的调节作用。这些项目涵盖了从纳米级到生物级的范围。 全细胞和动物模型的分子相互作用。该计划涉及以下方面：1) TCR空间组织对T细胞应答的影响，2)改变了T细胞的分子结构 免疫突触与T细胞无能，3)芽胞1作为一种新的T细胞激活抑制物，4)调节 TFII-I对T细胞内钙信号的影响；5)TCR和共刺激信号对核因子-kB的调节。这些 五个项目支持了解调节细胞激活的分子机制的总体目标。 该项目是在一群核心调查人员多年的互动中发展起来的，他们在过去的几年里 两年来，新同事加入了进来。调查人员之间的互动正在蓬勃发展。这个 从详细的项目说明中可以明显看出小组成员之间的协同程度。 我们想了解T细胞对抗原的反应机制。了解这些机制 将导致开启或关闭有益或有害的免疫反应的方法。

The overarching goal of this Program is to understand the molecular mechanisms that regulate cell activation. Activation of lymphocytes through specific recognition of antigen poses narrowly balanced benefits and risks, and hence is subject to tight regulation. We know that some signals serve to modulate or terminate activation, while other signals induce cell unresponsiveness or death. The molecular mechanisms underlying the regulatory processes with different outcomes are unknown and largely undefined. The Program consists of five highly interactive projects involving six investigators, from five different departments of the University. These investigators bring innovative technology and incisive ideas to bear on the problem of lymphocyte activation and its regulation. The five projects cover a range of stimuli, cues and outcomes that result in various states of T cell activation or unresponsiveness, from the initial events of antigen recognition to the regulation of transcription. The projects cover a biological scale from nano-scale molecular interactions to whole cell and animal models. The program addresses the following areas: 1) Influence of TCR spatial organization on T cell responses, 2) Altered molecular architecture at the Immunological Synapse and T cell anergy, 3) Sprouty 1 as a novel inhibitor of T cell activation, 4) Regulation of calcium signaling in T cells by TFII-I, 5) Regulation of NF-kB by TCR and costimulatory signaling. These five projects support the overall goal of understanding the molecular mechanisms regulating cell activation. The program has developed out of years of interaction among a core group of investigators who in the last two years have been joined by new colleagues. Interactions between investigators are flourishing. The extent of synergy between group members is apparent from the detailed project descriptions. We want to understand the mechanisms of T cell responses to antigen. Understanding these mechanisms will lead to ways of turning up, or turning off immune responses that are helpful or harmful.