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The Vα14 invariant natural killer T cell TCR forces microbial glycolipids and CD1d into a conserved binding mode

Invariant natural killer T cells (iNKT cells) rapidly produce effector cytokines. In this study, we report the first crystal structures of the iNKT cell T cell receptor (TCR) bound to two natural, microbial glycolipids presented by CD1d. Binding of the TCR induced CDR3-α–dependent structural changes...

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Autores principales: Li, Yali, Girardi, Enrico, Wang, Jing, Yu, Esther Dawen, Painter, Gavin F., Kronenberg, Mitchell, Zajonc, Dirk M.
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2010
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2964572/
https://www.ncbi.nlm.nih.gov/pubmed/20921281
http://dx.doi.org/10.1084/jem.20101335
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author Li, Yali
Girardi, Enrico
Wang, Jing
Yu, Esther Dawen
Painter, Gavin F.
Kronenberg, Mitchell
Zajonc, Dirk M.
author_facet Li, Yali
Girardi, Enrico
Wang, Jing
Yu, Esther Dawen
Painter, Gavin F.
Kronenberg, Mitchell
Zajonc, Dirk M.
author_sort Li, Yali
collection PubMed
description Invariant natural killer T cells (iNKT cells) rapidly produce effector cytokines. In this study, we report the first crystal structures of the iNKT cell T cell receptor (TCR) bound to two natural, microbial glycolipids presented by CD1d. Binding of the TCR induced CDR3-α–dependent structural changes in the F′ roof of CD1d; these changes resemble those occurring in the absence of TCR engagement when the highly potent synthetic antigen α-galactosylceramide (α-GalCer) binds CD1d. Furthermore, in the Borrelia burgdorferi α–galactosyl diacylglycerol–CD1d complex, TCR binding caused a marked repositioning of the galactose sugar into an orientation that closely resembles α-GalCer. The TCR-dependent reorientation of the sugar, together with the induced CD1d fit, may explain the weaker potency of the microbial antigens compared with α-GalCer. We propose that the TCR of iNKT cells binds with a conserved footprint onto CD1d, regardless of the bound glycolipid antigen, and that for microbial antigens this unique binding mode requires TCR-initiated conformational changes.
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spelling pubmed-29645722011-04-25 The Vα14 invariant natural killer T cell TCR forces microbial glycolipids and CD1d into a conserved binding mode Li, Yali Girardi, Enrico Wang, Jing Yu, Esther Dawen Painter, Gavin F. Kronenberg, Mitchell Zajonc, Dirk M. J Exp Med Article Invariant natural killer T cells (iNKT cells) rapidly produce effector cytokines. In this study, we report the first crystal structures of the iNKT cell T cell receptor (TCR) bound to two natural, microbial glycolipids presented by CD1d. Binding of the TCR induced CDR3-α–dependent structural changes in the F′ roof of CD1d; these changes resemble those occurring in the absence of TCR engagement when the highly potent synthetic antigen α-galactosylceramide (α-GalCer) binds CD1d. Furthermore, in the Borrelia burgdorferi α–galactosyl diacylglycerol–CD1d complex, TCR binding caused a marked repositioning of the galactose sugar into an orientation that closely resembles α-GalCer. The TCR-dependent reorientation of the sugar, together with the induced CD1d fit, may explain the weaker potency of the microbial antigens compared with α-GalCer. We propose that the TCR of iNKT cells binds with a conserved footprint onto CD1d, regardless of the bound glycolipid antigen, and that for microbial antigens this unique binding mode requires TCR-initiated conformational changes. The Rockefeller University Press 2010-10-25 /pmc/articles/PMC2964572/ /pubmed/20921281 http://dx.doi.org/10.1084/jem.20101335 Text en © 2010 Li et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).
spellingShingle Article
Li, Yali
Girardi, Enrico
Wang, Jing
Yu, Esther Dawen
Painter, Gavin F.
Kronenberg, Mitchell
Zajonc, Dirk M.
The Vα14 invariant natural killer T cell TCR forces microbial glycolipids and CD1d into a conserved binding mode
title The Vα14 invariant natural killer T cell TCR forces microbial glycolipids and CD1d into a conserved binding mode
title_full The Vα14 invariant natural killer T cell TCR forces microbial glycolipids and CD1d into a conserved binding mode
title_fullStr The Vα14 invariant natural killer T cell TCR forces microbial glycolipids and CD1d into a conserved binding mode
title_full_unstemmed The Vα14 invariant natural killer T cell TCR forces microbial glycolipids and CD1d into a conserved binding mode
title_short The Vα14 invariant natural killer T cell TCR forces microbial glycolipids and CD1d into a conserved binding mode
title_sort vα14 invariant natural killer t cell tcr forces microbial glycolipids and cd1d into a conserved binding mode
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2964572/
https://www.ncbi.nlm.nih.gov/pubmed/20921281
http://dx.doi.org/10.1084/jem.20101335
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