Dynein-Driven Transport of T Cell Receptor Microclusters Regulates Immune Synapse Formation and T Cell Activation
Dynein-Driven Transport of T Cell Receptor Microclusters Regulates Immune Synapse Formation and T Cell Activation
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DOI：
10.1016/j.immuni.2011.05.012
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发表时间：
2011-06-24
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：
Hashimoto-Tane, Akiko;Yokosuka, Tadashi;Saito, Takashi
当T细胞识别抗原呈递细胞（APC）上的肽-主要组织相容性复合物时，产生T细胞受体微簇（TCR-MCs）并移动到T细胞-APC界面的中心以形成中心超分子活化簇（cSMAC）。cSMAC的形成依赖于刺激强度并调节T细胞活化。我们证明了动力蛋白运动复合物与TCR复合物共定位和共免疫沉淀，TCR-MCs以动力蛋白依赖的方式沿沿着微管（MT）向免疫突触中心移动，形成cSMAC。MT位于激活位点处的质膜附近。TCR-MC速度和cSMAC形成受损的动力蛋白或MT抑制剂或动力蛋白表达的消融。具有受损cSMAC形成的T细胞表现出增强的细胞活化，包括蛋白磷酸化和白细胞介素-2产生。这些结果表明，通过TCR-MC运动形成cSMAC依赖于动力蛋白和MT，并且运动调节T细胞活化。
When T cells recognize a peptide-major histocompatibility complex on antigen-presenting cells (APCs), T cell receptor microclusters (TCR-MCs) are generated and move to the center of the T cell-APC interface to form the central supramolecular activation cluster (cSMAC). cSMAC formation depends on stimulation strength and regulates T cell activation. We demonstrate that the dynein motor complex colocalized and coimmunoprecipitated with the TCR complex and that TCR-MCs moved along microtubules (MTs) toward the center of the immune synapse in a dynein-dependent manner to form cSMAC. MTs are located in close proximity to the plasma membrane at the activation site. TCR-MC velocity and cSMAC formation were impaired by dynein or MT inhibitors or by ablation of dynein expression. T cells with impaired cSMAC formation exhibited enhanced cellular activation including protein phosphorylation and interleukin-2 production. These results indicate that cSMAC formation by TCR-MC movement depends on dynein and MTs, and the movement regulates T cell activation.