Spatiotemporal regulation of T cell costimulation by TCR-CD28 microclusters and protein kinase C theta translocation.
Spatiotemporal regulation of T cell costimulation by TCR-CD28 microclusters and protein kinase C theta translocation.
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DOI：
10.1016/j.immuni.2008.08.011
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发表时间：
2008-10-17
期刊：
影响因子：
32.4
通讯作者：
Saito, Takashi
中科院分区：
文献类型：
--
作者：
Yokosuka, Tadashi;Kobayashi, Wakana;Sakata-Sogawa, Kumiko;Takamatsu, Masako;Hashimoto-Tane, Akiko;Dustin, Michael L.;Tokunaga, Makio;Saito, Takashi
T细胞活化由含有TCR、激酶和衔接子的微簇（MC）介导。尽管TCR-MC易位形成T细胞和抗原呈递细胞（APC）之间的免疫突触的中央超分子活化簇（c-SMAC），但MC易位在T细胞信号传导中的作用仍不清楚。在这里，我们发现MCs在c-SMAC中的积累对于T细胞共刺激是重要的。利用平面双层膜系统，共刺激受体CD 28首先与TCR协同募集到MC，其信号通过与PKCθ的组装介导。它们的共定位和组装与共刺激功能相关。MCs在c-SMAC的聚集伴随着CD 28从TCR中的分离，并且CD 28和PKCθ都移位到c-SMAC的空间上独特的亚区。因此，共刺激是通过在c-SMAC中经由MC易位的动态调节产生新的共刺激隔室来介导的。
T cell activation is mediated by microclusters (MCs) containing TCRs, kinases, and adaptors. Although TCR-MCs translocate to form a central supramolecular activation cluster (c-SMAC) of immunological synapse between T cells and antigen-presenting cells (APCs), the role of MC translocation in T cell signaling remains unclear. Here, we found that the accumulation of MCs in c-SMAC was important for T cell co-stimulation. Using planar bilayer system, co-stimulatory receptor CD28 was initially recruited coordinately with TCR to MCs and its signals was mediated through the assembly with PKCθ. Their co-localization and assembly is correlated withco-stimulatory function. The accumulation of MCs at c-SMAC was accompanied by segregation of CD28 from TCRs and both CD28 and PKCθ translocated to a spatially unique sub-zone of c-SMAC. Thus, co-stimulation is mediated by generating a novel co-stimulatory compartment in c-SMAC via the dynamic regulation of MC translocation.
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DOI：
10.1084/jem.190.3.375
发表时间：
1999-08-02
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Holdorf AD;Green JM;Levin SD;Denny MF;Straus DB;Link V;Changelian PS;Allen PM;Shaw AS
通讯作者：
Shaw AS
影响因子：
5.4
作者：
Brossard, C;Feuillet, V;Trautmann, A
通讯作者：
Trautmann, A
影响因子：
64.8
作者：
Monks, CRF;Freiberg, BA;Kupfer, A
通讯作者：
Kupfer, A
影响因子：
30.5
作者：
Bromley, SK;Iaboni, A;Dustin, ML
通讯作者：
Dustin, ML
DOI：
10.1073/pnas.142298399
发表时间：
2002-07-09
影响因子：
11.1
作者：
Huang, JY;Lo, PF;Grey, HM
通讯作者：
Grey, HM