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lüll Dynamic regulation of T cell activation and co-stimulation through TCR-microclusters Saito T; Yokosuka T; Hashimoto-Tane AFEBS Lett 2010[Dec]; 584 (24): 4865-71TCR-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 PKCtheta 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.|*Lymphocyte Activation[MESH]|Animals[MESH]|Humans[MESH]|Receptors, Antigen, T-Cell/*immunology[MESH]|Signal Transduction[MESH]|T-Lymphocytes/*immunology[MESH] |