Laboratory for Cell Signaling, RIKEN Research Center for Allergy and Immunology, Yokohama, Kanagawa 230-0045, Japan.
Immunity. 2011 Jun 24;34(6):919-31. doi: 10.1016/j.immuni.2011.05.012.
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.
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，T 细胞受体微簇 (TCR-MC) 会生成，并移动到 T 细胞-APC 界面的中心，形成中央超分子激活簇 (cSMAC)。cSMAC 的形成取决于刺激强度，并调节 T 细胞的激活。我们证明了动力蛋白复合物与 TCR 复合物共定位并共免疫沉淀，并且 TCR-MC 沿着微管 (MT) 向免疫突触的中心以动力蛋白依赖性方式移动，以形成 cSMAC。MT 位于激活部位的质膜附近。动力蛋白或 MT 抑制剂或动力蛋白表达的缺失会损害 TCR-MC 的速度和 cSMAC 的形成。cSMAC 形成受损的 T 细胞表现出增强的细胞激活，包括蛋白质磷酸化和白细胞介素-2 的产生。这些结果表明，TCR-MC 运动形成 cSMAC 依赖于动力蛋白和 MT，并且该运动调节 T 细胞的激活。
