Chapter 13 - The Immunological Synapse

Abstract

The immunological synapse (IS) is a specialized cell-cell junction between a thymus-derived lymphocyte (T cell) and an antigen presenting cell (APC). Activation of T cells is based on the interaction between T cell receptors (TCRs) and major histocompatibility complex proteins that have bound antigenic peptides (MHCp). Because the TCR and MHCp are attached to the surface of the T cell and antigen-presenting cell (APC), respectively, the initiation of an immune response requires a molecular grasp between the T cell and APC—a synapse. A current focus of research on the IS is to determine how this supramolecular structure contributes to T-cell sensitivity and the fidelity of the T-cell response. Four areas in which the IS concept is contributing to our understanding of T-cell activation are coordination of antigen recognition and T-cell migration, role of the cytoskeleton in T-cell activation, mechanism of sensitive antigen recognition by T cells, and integration of the adaptive and innate immune responses. The IS concept provides a number of insights into the T-cell activation process. First, it provides a stop signal that coordinates antigen recognition and T-cell migration. Second, the essential role of the actin cytoskeleton in T-cell activation is related to the role of actin in IS formation. Third, the sensitivity of T cells to agonist MHCp is related to the role of weakly interacting, but probably more abundant, self MHCp in promoting IS formation. Finally, the IS provides a framework for orderly integration of the TCR and innate immune signals, such as in the case of CD28/CD80 interaction.