immune synapse

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immune synapse2016-12-25T07:21:18+00:00

immune synapse 

immune synapse image from New Medical Terms

immune synapse


Definition A specialised junction between antigen-presenting cells and effector immune responsive cells, in particular T- and natural killer cells, which consists of a central cluster of T cell receptors surrounded by concentric rings of proteins

Caption for image, quoted verbatim (minus references) This general concept of the molecular topography of the immunological-synapse platform is based on data obtained from different experimental models, and modifications of this probably underlie different types of contact region. The zone of T-cell receptor (TCR) signalling (central panel) is variably embedded between dynamic regions of high cytoskeletal turnover, which lead to membrane ruffling and position change (left panel), and more stable regions, which provide integrin-mediated adhesion and cytoskeletal strengthening (right panel). After TCR triggering by peptide–MHC complexes, the SRC-family kinase LCK is relocalized into lipid rafts and becomes activated. LCK activation is enhanced through co-stimulation by interactions between CD28 and CD80 or CD86. Activated LCK rapidly engages the SRC-family kinase FYN through tyrosine phosphorylation, and together, LCK and FYN phosphorylate consensus sites known as immunoreceptor tyrosine-based activation motifs (ITAMs) that are present in molecules such as the zeta-chain of CD3 and ZAP70 (zeta-chain-associated protein kinase of 70 kDa). Phosphorylated ITAMs function as docking sites for adaptor and signalling proteins. ZAP70 phosphorylates the raft-associated adaptor protein LAT (linker for activation of T cells), which functions as a platform for signalling molecules, including phospholipase C-gamma (PLC-gamma), phosphatidylinositol 3-kinase (PI3K) and SLP76 (SRC-homology-2-domain-containing leukocyte protein of 76 kDa). PLC-gamma liberates diacylglycerol (DAG) and inositol-1,4,5-trisphosphate (InsP3) from membrane phosphatidylinositol-4,5-bisphosphate (PtdIns(4,5)P2). DAG then activates protein kinase C-theta (PKC-theta), which is involved in the activation of the downstream transcription factors nuclear factor-kappaB (NF-kappaB) and activator protein 1 (AP1). PI3K converts PtdIns(4,5)P2 into phosphatidylinositol-3,4,5-trisphosphate (PtdIns(3,4,5)P3), which functions as a membrane scaffold for pleckstrin-homology-domain-containing proteins, such as AKT and WAVE (Wiskott–Aldrich syndrome protein (WASP)-family verprolin homologous protein). SLP76, AKT and WAVE support membrane-proximal actin dynamics and ruffling. In regions of more stringent adhesion, such as the peripheral supramolecular activation cluster (pSMAC), talin links interactions between LFA1 (lymphocyte function-associated antigen 1) and ICAM1 (intercellular adhesion molecule 1) to the actin cytoskeleton. Adhesive LFA1–ICAM1 interactions are induced by the RHO (RAS homologue)-family GTPase RAP1 (an important signalling molecule that can activate leukocyte integrins) through actin-filament strengthening. The transport of LFA1 out of the central SMAC (cSMAC) is thought to be mediated by the actin-binding protein talin. As well as actin filaments, microtubules and the microtubule-organizing centre (MTOC) polarize towards the immunological synapse and form a scaffold for vesicle transport. De-acetylated microtubules are initially maintained by histone deacetylase 6 (HDAC6), whereas acetylated microtubules, which are more stable, dominate at later time points. APC, antigen-presenting cell; NFAT, nuclear factor of activated T cells.

Immune synapse molecules

• c-SMAC (central-SMAC) composed of θ isoform of protein kinase C, CD2, CD4, CD8, CD28, Lck, Fyn.

• p-SMAC (peripheral-SMAC), composed of lymphocyte function-associated antigen-1 (LFA-1) and clustered cytoskeletal protein talin.

• d-SMAC (distal-SMAC), composed of CD43 and CD45

SMAC roles

• Regulate lymphocyte activation

• Transfer of peptide-MHC complexes from antigen-presenting cvells to lymphocytes

• Secretion of cytokines or lytic granules 

Synonyms Immunological synapse, SMAC, supramolecular adhesion complex

Note: Given the age of the image (2005), I expect to edit this shortly (JCS, 25.12.2016), in particular, to update names of genes that have been changed

Reference from
Nature Reviews Immunology 5, 532-545 (July 2005)

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