ublished data). LFA-1 is not required for mobility in T cell zones (Woolf et al., 2007), but LFA-1 increases sensitivity to MHC-peptide complexes up to 100-fold (Bachmann et al., 1997) and ICAM-1 is required for antigen specific arrest in vivo (Scholer et al., 2008). The lamellipodium is a sensory structure and has been shown to be the most sensitive part of a T cell by ~40-fold in elegant studies with laser traps and anti-CD3 coated beads (Negulescu et al., 1996; Wei et al., 1999). Valitutti has also described the probing behavior of lymphocytes undergoing sustained signaling on APCs (Valitutti et al., 1995a). Another important experiment is the demonstration that TCR signaling is continually being renewed by new TCR-MHC-peptide interactions such that blocking the access to new MHC-peptide ligands with MHC antibodies immediately block signaling (Valitutti et al., 1995a).
Lamellipodia are coordinated by small G-proteins including Rac-1, which activates the WAVE2 complexes leading to dynamic actin in the periphery 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, whi