Dynamic regulation of T cell activation and co-stimulation through TCR-microclusters |
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Authors: | Saito Takashi Yokosuka Tadashi Hashimoto-Tane Akiko |
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Institution: | Laboratory for Cell Signaling, RIKEN Research Center for Allergy and Immunology, Yokohama, Japan |
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Abstract: | 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. |
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Keywords: | T cell activation Microcluster Co-stimulation Lipid raft TCR complex Imaging |
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