Cytotoxic T lymphocytes form an antigen-independent ring junction

Immunological synapses are organized cell-cell junctions between T lymphocytes and APCs composed of an adhesion ring, the peripheral supramolecular activation cluster (pSMAC), and a central T cell receptor cluster, the central supramolecular activation cluster (cSMAC). In CD8 + cytotoxic T lymphocyt...

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Main Authors: Somersalo, K, Anikeeva, N, Sims, T, Thomas, V, Strong, R, Spies, T, Lebedeva, T, Sykulev, Y, Dustin, M
Format: Journal article
Language:English
Published: 2004
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author Somersalo, K
Anikeeva, N
Sims, T
Thomas, V
Strong, R
Spies, T
Lebedeva, T
Sykulev, Y
Dustin, M
author_facet Somersalo, K
Anikeeva, N
Sims, T
Thomas, V
Strong, R
Spies, T
Lebedeva, T
Sykulev, Y
Dustin, M
author_sort Somersalo, K
collection OXFORD
description Immunological synapses are organized cell-cell junctions between T lymphocytes and APCs composed of an adhesion ring, the peripheral supramolecular activation cluster (pSMAC), and a central T cell receptor cluster, the central supramolecular activation cluster (cSMAC). In CD8 + cytotoxic T lymphocytes, the immunological synapse is thought to facilitate specific killing by confining cytotoxic agents to the synaptic cleft. We have investigated the interaction of human CTLs and helper T cells with supported planar bilayers containing ICAM-1. This artificial substrate provides identical ligands to CD4+ and CD8+ T cells, allowing a quantitative comparison. We found that cytotoxic T lymphocytes form a ring junction similar to a pSMAC in response to high surface densities of ICAM-1 in the planar bilayer. MICA, a ligand for NKG2D, facilitated the ring junction formation at lower surface densities of ICAM-1. ICAM-1 and MICA are upregulated in tissues by inflammation- and stress-associated signaling, respectively. Activated CD8+ T cells formed fivefold more ring junctions than did activated CD4+ T cells. The ring junction contained lymphocyte function associated antigen-1 and talin, but did not trigger polarization and granule translocation to the interface. This result has specific implications for the mechanism of effective CTL hunting for antigen in tissues. Abnormalities in this process may alter CTL reactivity.
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spelling oxford-uuid:f4e48aaf-8f46-4925-ba53-18953d3b6b7d2022-03-27T12:23:13ZCytotoxic T lymphocytes form an antigen-independent ring junctionJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:f4e48aaf-8f46-4925-ba53-18953d3b6b7dEnglishSymplectic Elements at Oxford2004Somersalo, KAnikeeva, NSims, TThomas, VStrong, RSpies, TLebedeva, TSykulev, YDustin, MImmunological synapses are organized cell-cell junctions between T lymphocytes and APCs composed of an adhesion ring, the peripheral supramolecular activation cluster (pSMAC), and a central T cell receptor cluster, the central supramolecular activation cluster (cSMAC). In CD8 + cytotoxic T lymphocytes, the immunological synapse is thought to facilitate specific killing by confining cytotoxic agents to the synaptic cleft. We have investigated the interaction of human CTLs and helper T cells with supported planar bilayers containing ICAM-1. This artificial substrate provides identical ligands to CD4+ and CD8+ T cells, allowing a quantitative comparison. We found that cytotoxic T lymphocytes form a ring junction similar to a pSMAC in response to high surface densities of ICAM-1 in the planar bilayer. MICA, a ligand for NKG2D, facilitated the ring junction formation at lower surface densities of ICAM-1. ICAM-1 and MICA are upregulated in tissues by inflammation- and stress-associated signaling, respectively. Activated CD8+ T cells formed fivefold more ring junctions than did activated CD4+ T cells. The ring junction contained lymphocyte function associated antigen-1 and talin, but did not trigger polarization and granule translocation to the interface. This result has specific implications for the mechanism of effective CTL hunting for antigen in tissues. Abnormalities in this process may alter CTL reactivity.
spellingShingle Somersalo, K
Anikeeva, N
Sims, T
Thomas, V
Strong, R
Spies, T
Lebedeva, T
Sykulev, Y
Dustin, M
Cytotoxic T lymphocytes form an antigen-independent ring junction
title Cytotoxic T lymphocytes form an antigen-independent ring junction
title_full Cytotoxic T lymphocytes form an antigen-independent ring junction
title_fullStr Cytotoxic T lymphocytes form an antigen-independent ring junction
title_full_unstemmed Cytotoxic T lymphocytes form an antigen-independent ring junction
title_short Cytotoxic T lymphocytes form an antigen-independent ring junction
title_sort cytotoxic t lymphocytes form an antigen independent ring junction
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AT anikeevan cytotoxictlymphocytesformanantigenindependentringjunction
AT simst cytotoxictlymphocytesformanantigenindependentringjunction
AT thomasv cytotoxictlymphocytesformanantigenindependentringjunction
AT strongr cytotoxictlymphocytesformanantigenindependentringjunction
AT spiest cytotoxictlymphocytesformanantigenindependentringjunction
AT lebedevat cytotoxictlymphocytesformanantigenindependentringjunction
AT sykulevy cytotoxictlymphocytesformanantigenindependentringjunction
AT dustinm cytotoxictlymphocytesformanantigenindependentringjunction