Programmed cell death 1 forms negative costimulatory microclusters that directly inhibit T cell receptor signaling by recruiting phosphatase SHP2.
Programmed cell death 1 forms negative costimulatory microclusters that directly inhibit T cell receptor signaling by recruiting phosphatase SHP2.
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DOI：
10.1084/jem.20112741
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发表时间：
2012-06-04
期刊：
影响因子：
--
通讯作者：
Saito T
中科院分区：
文献类型：
--
作者：
Yokosuka T;Takamatsu M;Kobayashi-Imanishi W;Hashimoto-Tane A;Azuma M;Saito T
在遇到配体后，PD-1易位进入TCR微团簇，在那里它短暂地招募SHP2并抑制TCR信号组分的磷酸化和TCR驱动的停止信号。程序性细胞死亡1 （PD-1）是一种负性共刺激受体，对体外和体内T细胞活化的抑制至关重要。单细胞成像揭示了pd -1介导的抑制的分子机制。PD-1在与其配体PD-L1结合后与T细胞受体（TCRs）聚集，并与磷酸酶SHP2 （Src同源2结构域酪氨酸磷酸酶2）短暂相关。这些负性共刺激微团簇诱导近端TCR信号分子的去磷酸化。这导致T细胞活化的抑制和tcr诱导的停止信号的阻断。除了PD-1聚类外，微簇内PD-1 - tcr的共定位对于PD-1介导的有效抑制也是必需的。这种抑制机制在体内生成的PD-1hi T细胞中也起作用，并且可以被中和的抗pd - l1抗体覆盖。因此，PD-1微团簇的形成对T细胞活化的调控很重要。
After encounter with its ligand, PD-1 translocates into TCR microclusters, where it transiently recruits SHP2 and suppresses phosphorylation of TCR signaling components and TCR-driven stop signals. Programmed cell death 1 (PD-1) is a negative costimulatory receptor critical for the suppression of T cell activation in vitro and in vivo. Single cell imaging elucidated a molecular mechanism of PD-1–mediated suppression. PD-1 becomes clustered with T cell receptors (TCRs) upon binding to its ligand PD-L1 and is transiently associated with the phosphatase SHP2 (Src homology 2 domain–containing tyrosine phosphatase 2). These negative costimulatory microclusters induce the dephosphorylation of the proximal TCR signaling molecules. This results in the suppression of T cell activation and blockade of the TCR-induced stop signal. In addition to PD-1 clustering, PD-1–TCR colocalization within microclusters is required for efficient PD-1–mediated suppression. This inhibitory mechanism also functions in PD-1hi T cells generated in vivo and can be overridden by a neutralizing anti–PD-L1 antibody. Therefore, PD-1 microcluster formation is important for regulation of T cell activation.
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影响因子：
4.4
作者：
Chemnitz, JM;Parry, RV;Riley, JL
通讯作者：
Riley, JL
影响因子：
30.5
作者：
Latchman, Y;Wood, CR;Freeman, GJ
通讯作者：
Freeman, GJ
影响因子：
64.8
作者：
Monks, CRF;Freiberg, BA;Kupfer, A
通讯作者：
Kupfer, A
DOI：
10.1084/jem.20090847
发表时间：
2009-12-21
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Francisco LM;Salinas VH;Brown KE;Vanguri VK;Freeman GJ;Kuchroo VK;Sharpe AH
通讯作者：
Sharpe AH
影响因子：
32.4
作者：
Nishimura, H;Nose, M;Honjo, T
通讯作者：
Honjo, T