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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...
Autores principales: | , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
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The Rockefeller University Press
2010
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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. |
format | Text |
id | pubmed-2964572 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2010 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
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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