a fide MHC-peptide ligands? Signaling of T cells in response to anti-CD3ε is not blocked by depolymerizatin of F-actin (Valitutti et al., 1995a). Similarly, knock-down of the WAVE2 complex completely eliminates lamellipodial F-actin, but doesn’t inhibit early T cell signaling (Nolz et al., 2006). All but the largest TCR microclusters formed with MHC-peptide ligands are dissolved by depolymerization of F-actin (Varma et al., 2006). Nonetheless, the spreading of Jurkat cells on surfaces coated by anti-CD3ε is accompanied by the formation of a dramatic lamellipodial F-actin ring (Bunnell et al., 2001) and the formation of many discrete TCR microclusters throughout the interface that require F-actin to form in the normal manner (Bunnell et al., 2002). These structures recruit ZAP-70 and SLP-76 and, interestingly, the SLP-76 foci dissociate from the ZAP-70 rich TCR clusters and stream toward the center of the interface based on a mixture of F-actin and microtubule dependent transport processes and appear to engage in sustained signaling even after internalization (Barr et al., 2006; Bunnell et al., 2006) Nguyen et al, 2008). This behavior is strikingly similar to the observed movement of MHC-peptide based TCR microclusters, which occurs in the plane of the plasma membrane in the synapse (Varma et al., 2006). However, the anti-CD3ε driven TCR clusters become systematically F-actin independent after formation (Douglass and Vale, 2005). The inclusion of β1 integrin ligands like fibronectin on the surface with anti-CD3ε results in stabilization of the SLP-76 interaction with the TCR clusters and also appears to dampen F-actin dynamics (Nguyen et al., 2008). Integrin ligands generally enhance TCR signaling (Shimizu et al., 1990) and this study suggests that one component of this effect may be stabilization of TCR signaling complexes. There are clearly differences between the polyvalent anti-CD3ε interaction with the TCR complex, which contains two copies of the CD3ε chain (Call et al., 2002), and the monovalent interaction