Transient protein accumulation at the center of the T cell antigen presenting cell interface drives efficient IL-2 secretion
Transient protein accumulation at the center of the T cell antigen presenting cell interface drives efficient IL-2 secretion
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T 细胞抗原呈递细胞界面中心的瞬时蛋白质积累驱动高效的 IL-2 分泌
DOI：
10.1101/296616
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发表时间：
2018
期刊：
影响因子：
--
通讯作者：
Clark D
中科院分区：
文献类型：
--
作者：
Clark D
超分子信号组装体因其独特的信号传导特性而备受关注。一个微米级的信号组装，中央超分子信号簇（cSMAC），形成在抗原呈递细胞激活的T细胞界面的中心。我们已经确定它是由多个超分子体积高达0.5 µ m3的复合物组成，并与广泛的膜起伏有关。为了确定cSMAC功能，我们系统地操纵了三个衔接蛋白LAT、SLP-76和Grb 2的定位。cSMAC定位在衔接子之间变化，并且在共刺激受体CD 28的阻断和信号放大激酶Itk的缺乏后减少。cSMAC定位的重建恢复了IL-2分泌，这是依赖于重建动力学的关键T细胞效应子功能。我们的数据表明，cSMAC通过促进信号传导相互作用增强早期信号传导，并通过隔离一组更有限的信号传导中间体减弱此后的信号传导。
Supramolecular signaling assemblies are of interest for their unique signaling properties. A µm scale signaling assembly, the central supramolecular signaling cluster (cSMAC), forms at the center of the interface of T cells activated by antigen-presenting cells. We have determined that it is composed of multiple complexes of a supramolecular volume of up to 0.5 µm3and associated with extensive membrane undulations. To determine cSMAC function, we have systematically manipulated the localization of three adaptor proteins, LAT, SLP-76, and Grb2. cSMAC localization varied between the adaptors and was diminished upon blockade of the costimulatory receptor CD28 and deficiency of the signal amplifying kinase Itk. Reconstitution of cSMAC localization restored IL-2 secretion which is a key T cell effector function as dependent on reconstitution dynamics. Our data suggest that the cSMAC enhances early signaling by facilitating signaling interactions and attenuates signaling thereafter through sequestration of a more limited set of signaling intermediates.