Mechanism of T cell activation regulation by TCR microclusters and the costimulation network.
Project/Area Number |
24590590
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
Immunology
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Research Institution | Tokyo Medical University (2015) The Institute of Physical and Chemical Research (2012-2014) |
Principal Investigator |
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Project Period (FY) |
2012-04-01 – 2016-03-31
|
Project Status |
Completed (Fiscal Year 2015)
|
Budget Amount *help |
¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2013: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2012: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
|
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.
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Report
(5 results)
Research Products
(30 results)
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[Journal Article] Clustering of CARMA1 through SH3-GUK domain interactions is required for its activation of NF-kB signaling2015
Author(s)
Hara, H., Yokosuka, T., Hirakawa, H., Ishihara, C., Yasukawa, S., Yamazaki, M., Koseki, H., Yoshida, H. and Saito, T.
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Journal Title
Nat. Commun.
Volume: 6
Issue: 1
Pages: 5555-5555
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Journal Article] The lymphoid lineage-specific actin-uncapping protein Rltpr is essential for costimulation via CD28 and the development of regulatory T cells2013
Author(s)
Liang, Y., Cucchetti, M., Roncagalli, R., Yokosuka, T., Malzac, A., Bertosio, E., Imbert, J., Nijman, I.J., Suchanek, M., Saito, T., Wulfing, C., Malissen, B., Malissen, M.
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Journal Title
Nat. Immunol.
Volume: 14
Issue: 8
Pages: 858-866
DOI
Related Report
Peer Reviewed
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