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Publication : Dynein-driven transport of T cell receptor microclusters regulates immune synapse formation and T cell activation.

First Author  Hashimoto-Tane A Year  2011
Journal  Immunity Volume  34
Issue  6 Pages  919-31
PubMed ID  21703543 Mgi Jnum  J:173992
Mgi Id  MGI:5050758 Doi  10.1016/j.immuni.2011.05.012
Citation  Hashimoto-Tane A, et al. (2011) Dynein-driven transport of T cell receptor microclusters regulates immune synapse formation and T cell activation. Immunity 34(6):919-31
abstractText  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.
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