T淋巴细胞的发育分化受到分子水平上的精细调控，相关研究一直是免疫学研究的重点和热点。本课题组在前期研究中发现了一个调控T细胞发育的新基因TSE3（Thymocytes- Specific Expression， number 3），小鼠中该基因的缺失导致了T细胞发育受损。进一步研究表明，TSE3能与pLCg1和Grb2相互作用，且TSE3缺失导致TCR信号复合物形成减弱，预示TSE3参与TCR信号传导。本课题将进一步分析TSE3缺失对TCR信号传导的影响；揭示TSE3与pLCg1和Grb2相互作用的分子机制；同时探讨与TSE3相互作用的其它蛋白及TSE3在TCR活化过程中的磷酸化修饰，以及这些相互作用与修饰在TCR信号传导中的作用。上述研究可望为现有的TCR信号传导和T 细胞分化发育机制假说提供补充，从而为阐明临床上相关T 淋巴细胞功能缺陷性疾病的发病机制及其治疗提供理论依据。

Thymocyte development is tightly regulated at the molecular level, which is also a hot research area in recent years. We have previously identified a new molecule involved in T cell development named TSE3(Thymocyts-specific Expression, number 3). TSE3-/- mice demonstrated impaired thymocyte development. Further analysis revealed that TSE3 is associated with TCR signaling components including PLC-g1 and Grb2. We also showed that TSE3 deficiency impaired the assembly of TCR signalosome essential for TCR signaling suggesting the involvement of TSE3 in TCR signaling. This proposal will continue our study on the role of TSE3 in TCR signal transduction, detailed mapping of the protein-protein interaction domains in PLCg1 and Grb2. We will also put efforts on the identification of TSE3-binding proteins and the phosphorylation sites of TSE3 by using Tandem affinity purification and Mass spectrometry analysis. The completion of this project might provide us new insights into the current model of TCR signaling and thymocyte development and help the diagnosis and treatment of related immunodeficiency diseases.