cts with acidic phospholipids in the inner leaflet and facilitates the docking of both tyrosines in the lipid bilayer where they cannot be phosphorylated. The results suggest that a change in the lipid environment to a more neutral composition is needed for ITAM access by Src family kinases (Douglass and Vale, 2005). How could a single MHC-peptide complex change the lipid environment of the TCR?
Our understanding of the basal distribution of the TCR is constrained by two seemingly contradictory results: evidence for preclustering from electron microscopy (Schamel et al., 2005) and non-correlated monomeric diffusion using fluorescence correlation spectroscopy (James et al., 2007). Long term tracking of Fce receptor movements in the context of actin bundles on rat basophilic leukemia cells shows that receptors can be corralled by actin and diffuse independently at the same time (Andrews et al., 2008). These results suggest that the clusters seen in EM maybe a result of transient confinement on monomeric receptors. Basal fluctuations in TCR density were observed as highly dynamic structures similar in size to microclusters, but which could not be tracked from one frame to the next (Varma et al., 2006). In order to maintain low basal activity the membrane domains in which the TCR moves prior to ligand binding will likely be highly acidic and fluid.
The lamellipodium is a relatively flat membrane region with a dense mesh of branched actin filaments translocating away from the leading edge (Svitkina et al., 1997). The mesh size of the actin gel if relatively fine, with interstitial areas on the order of 100 nm based on electron microscopy analysis of model lamellipodia (Svitkina et al., 1997). This F-actin mesh is similar in scale to the lipids domains that have been identified in membranes as lipid rafts (Sharma et al., 2004). The spatial distribution of acidic lipids like PS on the inner leaflet is not known, but structural constrains suggest that liquid ordered domains should be enriched in neutral phosphatidylethan