The microsynapse is an essential structure for T cell activation

2014 Fiscal Year Final Research Report

• Project/Area Number: 24590591
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Immunology
• Research Institution: The Institute of Physical and Chemical Research
• Principal Investigator: HASHIMOTO-TANE Akiko 独立行政法人理化学研究所, 統合生命医科学研究センター, 研究員 (10415226)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: T細胞 / 免疫シナプス / T細胞受容体 / 受容体クラスター / インテグリン / ミオシン / 蛍光イメージング / 全反射顕微鏡

Outline of Final Research Achievements

In this study, we tried to reveal the mechanism for translation of TCR stimulation strength through quantitative imaging analysis of TCR microcluster (TCR-MC), which is a minimum assemble to start T cell activation. We performed proteome analysis and fluorescent imaging, and found that each TCR-MC was transiently bordered by a ring of focal adhesion molecules during the initial stage of T cell activation. The ring structure, which we named the microsynapse, is composed of LFA-1 and focal adhesion molecules such as paxillin, Pyk2 and the core structure of the TCR-MC. The microsynapse is supported by integrin outside-in signals, F-actin and myosin II activity. Perturbation of the microsynapse induced impairment of TCR-MC formation, reduced SLP76 recruitment, and resulted in impaired cellular signaling and function in vitro and in vivo. Thus, the microsynapse supports weak TCR response through integrin outside-in signals and is a critical structure for T cell activation.

Free Research Field

免疫