![]() ![]() Early signaling events have been shown to occur in peripheral microclusters in the pSMAC that coalesce into the cSMAC in both T and B cell synapses ( Campi et al., 2005 Yokosuka et al., 2005 Varma et al., 2006 Depoil et al., 2008), and active tyrosine kinases were only detected early in CD4 synapse formation ( Lee et al., 2002). The precise site of signaling events leading to immune synapse formation has been controversial (for review see Dustin, 2009). Intriguingly, this turns out to be reminiscent of other areas of focused secretion and endocytosis, which form during cytokinesis and cilia formation in other cell types. The picture that is beginning to emerge is that the synapse is a focal point for both exocytosis and endocytosis, both of which are triggered by localized cell signaling at the plasma membrane. (1998) triggered much speculation as to the precise roles of these discrete areas with a great deal of work focused on how the cSMAC controls receptor activation and down-regulation. The beautiful images generated by Monks et al. (1998) termed these regions the central supramolecular activation complex (SMAC ) and peripheral SMAC (pSMAC), with the cSMAC defining the cluster of T cell receptor (TCR) and associated signaling proteins and the pSMAC a ring of tight adhesion between the cells. Synapses are formed between both T cells ( Dustin et al., 1998 Monks et al., 1998 Grakoui et al., 1999) and B cells ( Batista et al., 2001) with their cognate antigen-presenting cells (APCs), and both are characterized by a dramatic reorganization of the receptors involved in recognition and adhesion ( Fig. The immunological synapse has created a frenzy of research since the term was first coined by Bill Paul in 1994 to describe the directed secretion of cytokines into a “small space between the two interacting cells,” based on the work of Poo et al. The problem of bestowing specificity on secreted proteins seems to have been overcome by the formation of what has become known as the immunological synapse. Although the membrane-bound antigen receptors specifically recognize their target cells, this is not necessarily true for secreted proteins such as cytokines. Cells of the immune system communicate both by direct interactions via membrane-bound receptors and via secreted mediators from one cell to another. ![]()
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