T细胞受体信号通路中的负性调控因子是确保T细胞只被合适的抗原激活且不被过度活化，维护T细胞自稳和耐受及防止自身免疫性疾病发生的重要因素。 SARM因含SAM和 ARM两个结构域而得名，它是负调控天然免疫信号通路的重要接头蛋白。我们前期研究发现，SARM可被招募到T细胞免疫突触，TCR刺激诱导SARM发生酪氨酸磷酸化，超表达SARM抑制TCR信号通路，推测SARM负调控TCR信号。研究将鉴定招募SARM至免疫突触的上游招募蛋白及其蛋白激酶，分析SARM与招募蛋白的相互作用机制；进一步找出SARM负调控TCR通路的靶点蛋白，分析SARM对其调节机制，从而阐明SARM在TCR通路中的作用和机制。同时解析SARM蛋白复合物的组成并分析其功能和机制，探讨SARM信号复合物与TCR信号通路的相互作用。并利用原代T细胞和小鼠，诠释SARM在T细胞活化增殖及不应中的调节功能。

The negative regulators of T cell receptor (TCR) signaling pathway ensure that T cells respond to appropriate ligands and for the proper duration, thus maintain T cells hemostasis and tolerance and prevent autoimmune disease. SARM, named for harboring SAM and ARM domains, is an important negative adapter in innate immune signaling. In our preliminary study, we found SARM can be recruited to T cell immunological synapse and be tyrosine phosphorylated upon TCR stimulation, whereas overexpression SARM inhibited TCR signaling. Thus, we propose SARM is a negative regulator of TCR signaling pathway. To approve this, we will identify the TCR proximal protein that recruits SARM to immunological synapse and the tyrosine kinase for SARM, analyze association domains and phosphorylation sites on SARM, find the target protein of SARM, demonstrate the role of SARM in TCR signaling and the mechanism underlying. Meanwhile, we will investigate the composition of SARM complex in T cells by mass-spectrometry, further explore the TCR regulation on SARM and the role of SARM in TCR signaling. Human primary T cells and mice will be employed to reveal the function of SARM in T cell activation,proliferation and anergy. This research will help to enrich the theory of T cell immunology and supply reference for clinical diagnosis and treatment.