Synapse Formation in the Brain

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Science  25 Aug 2006:
Vol. 313, Issue 5790, pp. 1020
DOI: 10.1126/science.313.5790.1020a

A productive meeting of a T cell and an antigen-presenting cell results in the formation of an immunological synapse between the membranes of the two cells, a crucial step in promoting T cell activation. Concentrated within synapses are the adhesion protein LFA1, T cell receptors, peptide-MHC complexes, and downstream signalling components. Two concentric domains of the synapse have been characterized: peripheral and central supramolecular activation clusters (pSMACs and cSMACs). Although both domains can be observed in vitro, difficulty seeing them in vivo has prompted discussion of their importance in effective immune responses. Using a rat model with a documented immune response to virally infected astrocytes in the brain, Barcia et al. found that both CD4+ and CD8+ T cells were required for clearance of infected cells, although only CD8+ cells entered the brain parenchyma to establish close contact with astrocytes. These contacts exhibited features characteristic of immune synapse formation, including recruitment and phosphorylation of the intracellular tyrosine kinases Lck and ZAP70 and a membrane reorganization into intimate three-dimensional apposition. More striking was the detection of cSMAC- and pSMAC-like regions, defined by the central and peripheral distributions of the T cell receptor and LFA1, respectively. Typical synapse structures were seen both before and during the immune-mediated clearance of infected astrocytes, suggesting their direct involvement in the antiviral response. — SJS

J. Exp. Med. 203, 10.1084/jem.20060420 (2006).

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