Dynein-Driven Transport of T Cell Receptor Microclusters Regulates Immune Synapse Formation and T Cell Activation

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 sti...

Ausführliche Beschreibung

Gespeichert in:
Bibliographische Detailangaben
Veröffentlicht in:Immunity (Cambridge, Mass.) Mass.), 2011-06, Vol.34 (6), p.919-931
Hauptverfasser: Hashimoto-Tane, Akiko, Yokosuka, Tadashi, Sakata-Sogawa, Kumiko, Sakuma, Machie, Ishihara, Chitose, Tokunaga, Makio, Saito, Takashi
Format: Artikel
Sprache:eng
Schlagworte:
Online-Zugang:Volltext
Tags: Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
Beschreibung
Zusammenfassung: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. [Display omitted] ► The dynein complex is associated and colocalized with the TCR signaling complex ► TCR microclusters (MCs) move along microtubles to the center of immune synapse ► Inhibition of dynein or microtubules impairs TCR-MC transport and cSMAC formation ► T cell activation is negatively regulated by dynein-mediated TCR-MC transport
ISSN:1074-7613
1097-4180
DOI:10.1016/j.immuni.2011.05.012