Dynamic regulation of T cell activation and co-stimulation through TCR-microclusters.
TCR-microclusters (MC) are generated upon TCR stimulation prior to the immune synapse formation independently of lipid rafts. TCR-MCs contain receptors, kinases and adaptors, and function as the signaling unit for T cell activation. The TCR complex, but not the signaling molecules, is transported to the center to form cSMAC. The co-stimulation receptor CD28 joins the signaling region of cSMAC and recruits PKCθ and Carma1. CTLA-4 accumulates in the same region and competes with CD28 for negative regulation of T cell activation. T cell activation is therefore mediated by two spatially distinct signaling compartments: TCR signaling by the peripheral TCR-MC and co-stimulation signal by the central signaling cSMAC.
Laboratory for Cell Signaling, RIKEN Research Center for Allergy and Immunology, Tsurumi-ku, Yokohama, Japan. saito@rcai.riken.jp
Takashi
T
Saito
Tadashi
T
Yokosuka
Akiko
A
Hashimoto-Tane
D000818:Animals; D006801:Humans; D008213:Lymphocyte Activation; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000276:immunology*
D011948:Receptors, Antigen, T-Cell