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， activation.通过特异性识别抗原的淋巴细胞的激活， 利益和风险，因此受到严格的监管。我们知道，有些信号是用来调节或 终止激活，而其他信号诱导细胞无反应或死亡。的分子机制 具有不同结果的监管过程的基础是未知的，而且在很大程度上是不确定的。 该计划包括五个高度互动的项目，涉及六名调查人员，来自五个不同的 大学的部门。这些研究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节的问题。这五个项目涵盖了一系列的刺激，线索和 结果导致T细胞活化或无反应的各种状态，从最初的事件， 抗原识别对转录的调节。这些项目涵盖了从纳米级到生物级的 分子间相互作用与全细胞和动物模型。该方案涉及以下领域：1） TCR空间组织对T细胞应答的影响，2）TCR空间组织的分子结构改变， 免疫突触和T细胞无反应性，3）Sprouty 1作为T细胞活化的新型抑制剂，4）调节 5）TCR和共刺激信号对NF-κ B的调节。这些 五个项目支持了解调节细胞活化的分子机制的总体目标。 该计划是在一个核心调查小组多年互动的基础上发展起来的， 两年来，有新同事加入。调查人员之间的互动正在蓬勃发展。的 从详细的项目说明中可以明显看出小组成员之间协同作用的程度。 我们希望了解T细胞对抗原反应的机制。了解这些机制 会导致产生或关闭有益或有害的免疫反应。

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.