Human invariant NKT cells display alloreactivity instructed by invariant TCR-CD1d interaction and killer Ig receptors.

Invariant NKT (iNKT) cells are a subset of highly conserved immunoregulatory T cells that modify a variety of immune responses, including alloreactivity. Central to their function is the interaction of the invariant TCR with glycosphingolipid (GSL) ligands presented by the nonpolymorphic MHC class I...

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Main Authors: Patterson, S, Chaidos, A, Neville, D, Poggi, A, Butters, T, Roberts, I, Karadimitris, A
Format: Journal article
Language:English
Published: 2008
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author Patterson, S
Chaidos, A
Neville, D
Poggi, A
Butters, T
Roberts, I
Karadimitris, A
author_facet Patterson, S
Chaidos, A
Neville, D
Poggi, A
Butters, T
Roberts, I
Karadimitris, A
author_sort Patterson, S
collection OXFORD
description Invariant NKT (iNKT) cells are a subset of highly conserved immunoregulatory T cells that modify a variety of immune responses, including alloreactivity. Central to their function is the interaction of the invariant TCR with glycosphingolipid (GSL) ligands presented by the nonpolymorphic MHC class I molecule CD1d and their ability to secrete rapidly large amounts of immunomodulatory cytokines when activated. Whether iNKT cells, like NK and conventional T cells, can directly display alloreactivity is not known. We show in this study that human iNKT cells and APC can establish a direct cross-talk leading to preferential maturation of allogeneic APC and a considerably higher reactivity of iNKT cells cultured with allogeneic rather that autologous APC. Although the allogeneic activation of iNKT cells is invariant TCR-CD1d interaction-dependent, GSL profiling suggests it does not involve the recognition of disparate CD1d/GSL complexes. Instead, we show that contrary to previous reports, iNKT cells, like NK and T cells, express killer Ig receptors at a frequency similar to that of conventional T cells and that iNKT cell allogeneic activation requires up-regulation and function of activating killer Ig receptors. Thus, iNKT cells can display alloreactivity, for which they use mechanisms characteristic of both NK and conventional T cells.
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spelling oxford-uuid:29a29b92-3221-4a85-92a9-60f742c6c4a72022-03-26T12:20:19ZHuman invariant NKT cells display alloreactivity instructed by invariant TCR-CD1d interaction and killer Ig receptors.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:29a29b92-3221-4a85-92a9-60f742c6c4a7EnglishSymplectic Elements at Oxford2008Patterson, SChaidos, ANeville, DPoggi, AButters, TRoberts, IKaradimitris, AInvariant NKT (iNKT) cells are a subset of highly conserved immunoregulatory T cells that modify a variety of immune responses, including alloreactivity. Central to their function is the interaction of the invariant TCR with glycosphingolipid (GSL) ligands presented by the nonpolymorphic MHC class I molecule CD1d and their ability to secrete rapidly large amounts of immunomodulatory cytokines when activated. Whether iNKT cells, like NK and conventional T cells, can directly display alloreactivity is not known. We show in this study that human iNKT cells and APC can establish a direct cross-talk leading to preferential maturation of allogeneic APC and a considerably higher reactivity of iNKT cells cultured with allogeneic rather that autologous APC. Although the allogeneic activation of iNKT cells is invariant TCR-CD1d interaction-dependent, GSL profiling suggests it does not involve the recognition of disparate CD1d/GSL complexes. Instead, we show that contrary to previous reports, iNKT cells, like NK and T cells, express killer Ig receptors at a frequency similar to that of conventional T cells and that iNKT cell allogeneic activation requires up-regulation and function of activating killer Ig receptors. Thus, iNKT cells can display alloreactivity, for which they use mechanisms characteristic of both NK and conventional T cells.
spellingShingle Patterson, S
Chaidos, A
Neville, D
Poggi, A
Butters, T
Roberts, I
Karadimitris, A
Human invariant NKT cells display alloreactivity instructed by invariant TCR-CD1d interaction and killer Ig receptors.
title Human invariant NKT cells display alloreactivity instructed by invariant TCR-CD1d interaction and killer Ig receptors.
title_full Human invariant NKT cells display alloreactivity instructed by invariant TCR-CD1d interaction and killer Ig receptors.
title_fullStr Human invariant NKT cells display alloreactivity instructed by invariant TCR-CD1d interaction and killer Ig receptors.
title_full_unstemmed Human invariant NKT cells display alloreactivity instructed by invariant TCR-CD1d interaction and killer Ig receptors.
title_short Human invariant NKT cells display alloreactivity instructed by invariant TCR-CD1d interaction and killer Ig receptors.
title_sort human invariant nkt cells display alloreactivity instructed by invariant tcr cd1d interaction and killer ig receptors
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