Mechanism of T cell activation regulation by TCR microclusters and the costimulation network.

2015 Fiscal Year Final Research Report

• Project/Area Number: 24590590
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Immunology
• Research Institution: Tokyo Medical University (2015); The Institute of Physical and Chemical Research (2012-2014)
• Principal Investigator: Yokosuka Tadashi 東京医科大学, 医学部, 教授 (10359599)
• Project Period (FY): 2012-04-01 – 2016-03-31
• Keywords: 免疫学 / シグナル伝達 / 分子イメージング / T細胞受容体 / 補助刺激受容体

Outline of Final Research Achievements

The imaging analysis revealed a new insight that a negative costimulatory receptor, PD-1, accumulated at a T cell signalosome, the TCR microcluster, and recruited a phosphatase, SHP2, to suppress T cell activation in a ligand-binding manner. The anti-PD-1 antibody, whose an advantage in the immune check-point therapy, blocked the aggregation of PD-1 at the TCR microclusters, resulting in the recovery of T cell activation. An activating costimulatory receptor, ICOS, increased the translocation of PI3K at TCR microclusters through the binding to its ligands. These data demonstrate that T cell activation is spatiotemporally regulated by both activating and suppressive costimulation signalosomes.

Free Research Field

医歯薬学・基礎医学・免疫学