Spatiotemporal and structural analysis of T cell activation regulation

2017 Fiscal Year Final Research Report

• Project/Area Number: 24229004
• Research Category: Grant-in-Aid for Scientific Research (S)
• Allocation Type: Single-year Grants
• Research Field: Immunology
• Research Institution: Institute of Physical and Chemical Research
• Principal Investigator: Saito Takashi 国立研究開発法人理化学研究所, 統合生命医科学研究センター, グループディレクター (50205655)
• Co-Investigator(Kenkyū-buntansha): 多根 彰子 (橋本彰子) 国立研究開発法人理化学研究所, 統合生命医科学研究センター, 上級研究員 (10415226)
• Project Period (FY): 2012-05-31 – 2017-03-31
• Keywords: T細胞 / TCR-CD3複合体 / ミクロクラスター / シグナル伝達 / 細胞活性化 / イメージング解析

Outline of Final Research Achievements

T cell activation upon antigen recognition is found to be mediated by recruiting various signal molecules to TCR microclusters. The activation is regulated by several signals; positive and negative co-stimulation signals, innate signals, and cytoskeletal signals. We then analyzed spatiotemporal aspects of these regulations. Among them, we found the generation of inhibitory microclusters by inhibitory receptors PD-1 and new intracellular signaling sites for Ras activation. The structural basis of antigen recognition and activation through the TCR-CD3 complex has been tried to analyze by synthesis and structural analysis of whole molecules of the TCR-CD3 complex including intracellular domains. We have also clarified T cell activation status and their regulation of activation upon self-recognition by T cells in vivo.

Free Research Field

免疫学