endent down-regulation of CCR7. This gives the T cells flexibility in looking at different amounts of antigen on DCs-a few DCs with high amounts of MHC-peptide can stop T cells whereas many DCs with few antigen can sustain signaling until the T cells resets its sensitivity and can arrest (Henrickson et al., 2008). Weaker MHC-peptide never overcome the chemokinetic signals and continually migrate in DC networks (Skokos et al., 2007). T cells encountering these weaker ligands cannot arrest in the steady state and only integrate signals through kinapses. This mode of signal integration is sufficient to induce an alternative mode of tolerance induction when the antigen is presented on many DCs through scavenger receptor DEC-205. The failure of some weaker self-antigens to stop T cells may contribute the failure of tolerance induction and the development of autoimmuity (Zehn and Bevan, 2006). In autoimmunity the combination of strong innate signals and weak TCR signals can lead to robust responses, although there 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). Simila