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T-cell-antigen recognition and the immunological synapse

T-cell-antigen recognition and the immunological synapse The original meaning of the Greek term 'synapse' is probably best described as 'connection' or 'junction' between two similar entities. We define the 'immunological synapse' as any stable, flattened interface between a lymphocyte or natural killer cell and a cell that they are in the process of recognizing. Synapse formation is an energy-dependent process that causes a marked polarization of the T cell, involving cytoskeletal rearrangement, in particular the movement of the microtubule organizing centre (MTOC) from the rear end of the T cell to a location underneath the synapse. The mature immunological synapse is best described between T helper cells and their conjugated antigen-presenting cells (APCs), where it is organized in distinct areas, known as supra-molecular activation complexes (SMACs). The central SMAC (cSMAC) is enriched in T-cell receptors (TCR) and many of its accessory polypeptides and signalling molecules. Cell adhesion seems to predominate in a peripheral ring that surrounds the cSMAC (pSMAC) and bulky molecules accumulate in a region distal to the synapse (dSMAC) — that is, outside of the pSMAC. Co-stimulation, as provided through CD28–CD80/CD86 and leukocyte function-associated antigen 1 (LFA1)–intercellular adhesion molecule 1 (ICAM1) interactions, is required for molecular recruitment to the synapse, which is mediated through cytoskeletal mechanisms. Agrin and MGAT5 have recently been described as genes that influence the degree of molecular segregation. The role of the size of the extracellular domain of synapse-localized membrane proteins in large-scale patterning is presently debated. TCR-proximal signalling precedes the formation of the mature immunological synapse and is most marked before its formation, however, TCR-mediated signals do not only continue throughout the lifetime of the synapse but also actively maintain the synapse. Premature abrogation of later TCR signals markedly affects the response of the T cell. Advances in imaging technology make it increasingly possible to study the dynamics of synapse formation in vivo (in lymph nodes, thymus, for example). At present, there is a debate over the duration of such interactions as they occur in the course of T-cell priming. Although most studies deal with the synapse between effector T helper cells and B-cell tumour lines, the field is now moving towards more specialized scenarios. Considerable 'deviations from the rule' become increasingly evident and highlight the physiological and developmental context as well as location in the body in which antigenic information is conveyed through the immunological synapse. With increasing research devoted to the immune synapse, its function is presently under scrutiny. A recent study describes it as a 'servo-controller' that boosts T-cell sensitivity and attenuates strong signals. In addition, we envision the immune synapse as a platform that provides sufficient regulatory mechanisms which are required to guide T-cell activity in accordance with its developmental stage, its range of functions, the nature of the APC involved, as well as both the quality and quantity of TCR ligands involved. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Nature Reviews Immunology Springer Journals

T-cell-antigen recognition and the immunological synapse

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References (83)

Publisher
Springer Journals
Copyright
Copyright © 2003 by Nature Publishing Group
Subject
Biomedicine; Biomedicine, general; Immunology
ISSN
1474-1733
eISSN
1474-1741
DOI
10.1038/nri1245
Publisher site
See Article on Publisher Site

Abstract

The original meaning of the Greek term 'synapse' is probably best described as 'connection' or 'junction' between two similar entities. We define the 'immunological synapse' as any stable, flattened interface between a lymphocyte or natural killer cell and a cell that they are in the process of recognizing. Synapse formation is an energy-dependent process that causes a marked polarization of the T cell, involving cytoskeletal rearrangement, in particular the movement of the microtubule organizing centre (MTOC) from the rear end of the T cell to a location underneath the synapse. The mature immunological synapse is best described between T helper cells and their conjugated antigen-presenting cells (APCs), where it is organized in distinct areas, known as supra-molecular activation complexes (SMACs). The central SMAC (cSMAC) is enriched in T-cell receptors (TCR) and many of its accessory polypeptides and signalling molecules. Cell adhesion seems to predominate in a peripheral ring that surrounds the cSMAC (pSMAC) and bulky molecules accumulate in a region distal to the synapse (dSMAC) — that is, outside of the pSMAC. Co-stimulation, as provided through CD28–CD80/CD86 and leukocyte function-associated antigen 1 (LFA1)–intercellular adhesion molecule 1 (ICAM1) interactions, is required for molecular recruitment to the synapse, which is mediated through cytoskeletal mechanisms. Agrin and MGAT5 have recently been described as genes that influence the degree of molecular segregation. The role of the size of the extracellular domain of synapse-localized membrane proteins in large-scale patterning is presently debated. TCR-proximal signalling precedes the formation of the mature immunological synapse and is most marked before its formation, however, TCR-mediated signals do not only continue throughout the lifetime of the synapse but also actively maintain the synapse. Premature abrogation of later TCR signals markedly affects the response of the T cell. Advances in imaging technology make it increasingly possible to study the dynamics of synapse formation in vivo (in lymph nodes, thymus, for example). At present, there is a debate over the duration of such interactions as they occur in the course of T-cell priming. Although most studies deal with the synapse between effector T helper cells and B-cell tumour lines, the field is now moving towards more specialized scenarios. Considerable 'deviations from the rule' become increasingly evident and highlight the physiological and developmental context as well as location in the body in which antigenic information is conveyed through the immunological synapse. With increasing research devoted to the immune synapse, its function is presently under scrutiny. A recent study describes it as a 'servo-controller' that boosts T-cell sensitivity and attenuates strong signals. In addition, we envision the immune synapse as a platform that provides sufficient regulatory mechanisms which are required to guide T-cell activity in accordance with its developmental stage, its range of functions, the nature of the APC involved, as well as both the quality and quantity of TCR ligands involved.

Journal

Nature Reviews Immunology – Springer Journals

Published: Dec 1, 2003

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