ple of the potential complexity can be seen in interaction networks recently compiled as the integrin adhesome (Zaidel-Bar et al., 2007).
Once the ITAMs are exposed Src family kinases can then initiate phosphorylation by diffusion into the same domain (Douglass and Vale, 2005)(Fig 2). Exclusion of CD45 in the nascent foci would increase the half-life of the phosphorylated ITAM allowing sufficient time for ZAP-70 recruitment (Varma et al., 2006). This cluster may interact more strongly with LAT so that ZAP-70 could phosphorylate LAT and Itk to initiate PLC-g recruitment and initiation of Ca2+ signaling, PKC activation and Ras-GRP recruitment. Integrin microclusters will be interspersed with the TCR microclusters. Integrin dependent signaling will generate additional diacylglycerol for RasGRP by activating phospholipase D and phosphatidic acid phosphatase (Mor et al., 2007). Electron micrographs of membrane sheets suggest that immunoreceptor rich and LAT rich islands only partially mix (Lillemeier et al., 2006; Wilson et al., 2001). The force needed to induce island mixing may be generated by periodic myosin II based contraction. This may account for the role of myosin IIA in the signal amplification from Lck, which is normally activated after myosin IIA knock-down, to ZAP-70 and LAT, which are only weakly activated in myosin IIA knock-down T cells (Ilani et al., 2009).
The TCR triggering process in microclusters and how this is sustained in a synapse has relevance to T cell decision-making. T cell differentiation is controlled in large part by cytokines and small molecules from APC. There are two independent reports that propose distinct mechanisms for the synapse to influence differentiation. One is the concentration of interferon-γ receptors in the synapse leading to increased T helper 1 (Th1) cell development (Maldonado et al., 2004). IL-4 counteracts this through Stat6 (Maldonado et al., 2004). The other is the control of polarity networks leading to asymmetric cell division to control memory-effector decision