The distal pole complex: a novel membrane domain distal to the immunological synapse

Summary: While much interest has focused on the finding that T cell–antigen presenting cell (APC) interaction induces the recruitment of proteins to the immunological synapse (IS), we have recently discovered that APC binding induces the formation of a novel protein complex distal to the site of T‐cell receptor ligation. This ‘distal pole complex’ (DPC) is important for appropriate T‐cell activation, functioning either to remove proteins from the synapse or as a signaling complex in its own right. The first component of the DPC to be identified was CD43, a cell‐surface mucin that has been proposed to function as a negative regulator of T‐cell signaling. CD43 movement was found to depend on ezrin and moesin, members of the ERM family, which serve to link CD43 and other cargo molecules to the actin cytoskeleton. ERM proteins interact with several other important surface receptors and cytoplasmic signaling molecules, some of which we have identified as additional components of the DPC. Disruption of the DPC leaves early T‐cell activation events intact but affects cytokine expression. Here, we review what is currently known about the formation and function of the DPC and speculate on how this novel protein complex serves to facilitate T‐cell activation.