Immunological Synapse

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.

Keywords: immunological synapse; T lymphocytes; T‐cell activation; T‐cell polarisation; T‐cell receptor; intracellular vesicle traffic; cytoskeletal interplay; TCR signalling

Figure 1. A variety of immune cell interactions form immunological synapses. Immunological synapses may form in lymphoid organs or in peripheral tissues. Dendritic cells capture antigens at the epithelia, get activated and migrate to lymph nodes, where they can present antigens to circulating T or B cells. T cells circulating through lymph nodes recognise processed antigen in complex with MHC class II molecules on dendritic cells (DCs). In contrast, B cells recognise native antigens displayed on the surface of follicular dendritic cells (fDCs). Upon interaction with those antigens, B cells get activated and internalise the antigen. Upon processing, B cells will present those antigens to T cells. Cytotoxic T cells and NK cells form lytic synapses with virus‐infected or tumour target cells, mostly in peripheral tissues.
Figure 2. T cells polarise towards APCs: (a) immunological synapse observed by scanning electron microscopy, T cell on top, shows asymmetric shape; (b) after engagement with the APC, the T cell changes shape, polarises the actin cytoskeleton microtubules and intracellular vesicle traffic (Golgi, endosomes and cytotoxic vesicles) towards the cell–cell contact zone. (Reproduced with permission from V. Robbiati and S. Guadagnini © Institut Pasteur.)
Figure 3. Main signalling pathways coupled to the TCR and co‐signalling molecules at the immunological synapse. Four main signalling pathways converge to the T‐cell nucleus for the activation of cytokine gene transcription. They are depicted here by colour codes: the Ca2+ calcineurin pathway in violet, the PKCθ pathway in golden orange, the Ras/ERK pathway in green and the Vav1‐Jun pathway in blue. Adaptor proteins are in greenish yellow.
Figure 4. Dynamics of signalling microclusters at the immunological synapse. Signalling microclusters form at the periphery of the synapse, and then migrate to the centre via an actin, myosin IIA and microtubule‐dependent movement. Then, TCR concentrates at the centre of synapse, whereas other signalling complexes are internalised or disassembled. (a) A scheme of a surrogate synapse of a T cell spreading on a planar lipid bilayer or an anti‐CD3 coated coverslip. (b) Confocal image of a T‐cell spread on anti‐CD3‐coated coverslip. Microtubules are stained in green and SLP76 in red. SLP76‐containing signalling microclusters are located along microtubules (arrow heads). (Reproduced with permission from Lasserre et al. (2010) © EMBO.)
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Further Reading

Carrasco YR (2010) Molecular and cellular dynamics at the early stages of antigen encounter: the B‐cell immunological synapse. Current Topics in Microbiology and Immunology 340: 51–62.

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Xie J, Tato CM and Davis MM (2013) How the immune system talks to itself: the varied role of synapses. Immunology Reviews 251 (1): 65–79.

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Agüera‐Gonzalez, Sonia, Bouchet, Jérôme, and Alcover, Andrés(Jun 2015) Immunological Synapse. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0004027.pub2]