T-cell-receptor-dependent Actin Regulatory Mechanisms

Following stimulation, T cells undergo marked changes in actin architecture that are required for productive immune responses. T-cell-receptor-dependent reorganization of the actin cytoskeleton is necessary for the formation of the immunological synapse at the T-cell-antigen-presenting-cell contact site and the distal pole complex at the opposite face of the T cell. Convergence of specific signaling molecules within these two plasma membrane domains facilitates downstream signaling events leading to full T-cell activation. Recent studies have identified many of the relevant actin-regulatory proteins, and significant progress has been made in our understanding of how these proteins choreograph molecular movements associated with T-cell activation. Proteins such as WASp, WAVE2, HS1 and cofilin direct the formation of a cortical actin scaffold at the immune synapse, while actin-binding proteins such as ezrin and moesin direct binding of signaling molecules to actin filaments within the distal pole complex.