Plasma membrane segregation during T cell activation: probing the order of domains

T cell activation leads to a segregation of plasma membrane domains to form TCR signalling clusters and eventually immunological synapses. At these T cell activation sites signalling protein networks reside in plasma membrane regions which adopt a highly ordered physical state. Studies of reconstituted model membranes suggest that aggregation of lipid raft-favouring membrane components may trigger this lipid ordering and condensation of membrane domains in T cells. Activation-induced protein–protein interactions such as anchorage to the cytoskeleton drive this condensation of the plasma membrane. Elucidating the functional role and specific molecular mechanisms of lipid ordering at these domains in the T cell activation cascade will be an essential element in understanding the transmission of outside signals into intracellular responses.