hery of nascent immunological synapses (Nolz et al., 2006). HS-1, a lymphocyte-specific cortactin is important for forming lamellipodia (Gomez et al., 2006). EVL, a hematopoietic cell member of the ENA-VASP family, is found at the tips of projections touching the APC (Lambrechts et al., 2000). Activation of these systems is not antigen specific and similar structures are induced during non-antigen specific engagement of adhesion molecule like LFA-1 by ICAM-1 (Smith et al., 2003) and CD2 by CD58 (or CD48 in the mouse) (Kaizuka et al., 2009). In response to TCR signals, the SLP-76 signaling module recruits and activates Vav, an exchange factor for Rac and Cdc42. Rac then activates WAVE2 and Cdc42 activates WASP. Both WAVE2 and WASP activate the Arp2/3 complex to generate branched actin networks. WAVE2 is associated with lamellipodial actin (Nolz et al., 2006), whereas WASP is associated with ventral projections such as podosomes and invadipodia (Carman et al., 2007). Behind the lamellipodium is the lamella, which has also been referred to as a focal zone in migrating T cells (Smith et al., 2005). These zones are rich in adhesion sites and integrin binding adapter talin, which is also a marker of the pSMAC. T cell may arrest migration and form a stable synapse, or alternatively, they may continue to migrate and integrate signals on the move. This rapid migration during antigen recognition contrasts with the stable synapse and has different functional consequences.
Rapid migration during antigen recognition is observed in T-DC interactions in vitro early stages of T cell interaction with low dose agonist stimuli in vivo (Henrickson et al., 2008) and with low potency TCR stimuli (Skokos et al., 2007). There are at least two explanations for these mobile junctions or “kinapses”(Dustin, 2008). Certain chemokinetic signals, such as CCL21 signals, can compete with antigen stop signals (Bromley et al., 2000). The ability of T cells to migrate for some period followed by arrest may relate to signaling thresholds or time dep