are differences in the kinetics of T cell release from lymph nodes and fitness of the cells that may limit memory generation autoimmunity (Zehn and Bevan, 2006). Thus, a migrating T cell sensing MHC-peptide complexes at its leading edge can integrate signals and make decisions about tolerance to abundant antigens, but not rare self-antigens.
How do T cells form a synapse? T cells stopped by MHC-peptide complexes remained highly dynamics with prominent cycles of extension and retraction around a pivot point (Dustin et al., 1997; Valitutti et al., 1995a). Studies on planar bilayers reveal what appears to be an early spreading, receptor engagement and contractile process that form the cSMAC over a period of 5 minutes and which is F-actin dependent (Grakoui et al., 1999). These results also led to speculation that myosin II based contraction might also be involved because of the substantial decreases in contact size and the speed of receptor cluster movement (Dustin and Cooper, 2000; Grakoui et al., 1999). Similar results were obtained in live cell-cell systems in which TCR in small clusters moved to the center to form the cSMAC (Krummel et al., 2000). However, these authors eventually rejected the hypothesis that myosin II is required for this contraction and transport process because knockdown of myosin IIA did not appear to eliminate the ability to form a synapse with an APC (Jacobelli et al., 2004). More recent studies in the planar bilayer model actually supported the hypothesis that myosin IIA is important for microcluster transport and signal amplification in that system and for signal amplification in cell-cell models (Ilani et al., 2009). It is possible that there are alternative mechanisms to form a cSMAC in cell-cell systems that involve directed vesicular transport, which would be myosin II independent (Das et al., 2004). Nonetheless, the extension of an APC embracing lamellipodium is observed in cell-cell systems (Antón et al., 2002; Tskvitaria-Fuller et al., 2003). In Jurkat T leukemia cells, spreading 