Immunological Synapse

Abstract

Abstract Immunological synapses are dynamically organised cell–cell interfaces formed between cells of the immune system. Different types of immunological synapses lead to distinct functional outcomes. Thus, T and B lymphocytes form immunological synapses with each other and with dendritic cells or macrophages, conveying mutual activation cues. Moreover, natural killer cells or cytotoxic T lymphocytes form synapses with tumour or infected cells delivering cytotoxic granules that destroy those anomalous cells. Immunological synapses are the result of an orchestrated cell polarisation process that involves cytoskeleton rearrangements, intracellular vesicle traffic and the clustering of receptors, adhesion molecules and signalling effectors, which together ensure the immunological synapse stability, its structure and function. Immunological synapses play key roles in immune responses, like T‐ and B‐cell activation, and polarised secretion of cytokines or cytotoxic granules. Key Concepts T cells recognise antigens as molecular fragments associated with major histocompatibility complex proteins displayed at the surface of antigen presenting cells. Immunological synapses are subcellular structures formed at the interface between T cells and antigen presenting cells. Immunological synapses regulate lymphocyte activation and effector functions, like polarised secretion of cytokines, or cytotoxic granules. T‐cell polarisation induced by T‐cell receptor engagement drives the formation of the immunological synapse and ensures its functions. The immunological synapse is characterised by the reorganisation of the T‐cell actin and microtubule cytoskeleton at the antigen presenting cell contact site. Intracellular vesicle traffic, including that of the Golgi apparatus, endosomes and lysosomes, polarises to the immunological synapse. Endosomal vesicles convey the T‐cell receptor and signalling molecules to the immunological synapse. The Golgi apparatus reorients towards the immunological synapse favouring the polarised secretion of cytokines from T cells to B cells. T‐cell receptor, co‐receptors, adhesion proteins and signalling molecules form dynamic clusters at the immunological synapse. Signalling microcluster dynamics regulate the T‐cell receptor signal transduction capacity.