A semi-invariant V{alpha}10{+} T cell antigen receptor defines a population of natural killer T cells with distinct glycolipid antigen-recognition properties

Adam Uldrich, Onisha Patel, Garth Cameron, Daniel Pellicci, E Bridie Day, Lucy Sullivan, Konstantinos Kyparissoudis, Lars Kjer-Nielsen, Julian Vivian, Benjamin Cao, Andrew Brooks, Spencer Williams, Petr Illarionov, Gurdyal Besra, Stephen Turner, Steven Porcelli, James McCluskey, Mark Smyth, Jamie Rossjohn, Dale Godfrey

Research output: Contribution to journalArticleResearchpeer-review

Abstract

Type I natural killer T cells (NKT cells) are characterized by an invariant variable region 14-joining region 18 (V(alpha)14-J(alpha)18) T cell antigen receptor (TCR) alpha-chain and recognition of the glycolipid alpha-galactosylceramide (alpha-GalCer) restricted to the antigen-presenting molecule CD1d. Here we describe a population of alpha-GalCer-reactive NKT cells that expressed a canonical V(alpha)10-J(alpha)50 TCR alpha-chain, which showed a preference for alpha-glucosylceramide (alpha-GlcCer) and bacterial alpha-glucuronic acid-containing glycolipid antigens. Structurally, despite very limited TCRalpha sequence identity, the V(alpha)10 TCR-CD1d-alpha-GlcCer complex had a docking mode similar to that of type I TCR-CD1d-alpha-GalCer complexes, although differences at the antigen-binding interface accounted for the altered antigen specificity. Our findings provide new insight into the structural basis and evolution of glycolipid antigen recognition and have notable implications for the scope and immunological role of glycolipid-specific T cell responses.
Original languageEnglish
Pages (from-to)616 - 623
Number of pages8
JournalNature Immunology
Volume12
Issue number7
DOIs
Publication statusPublished - 2011

Cite this

Uldrich, Adam ; Patel, Onisha ; Cameron, Garth ; Pellicci, Daniel ; Day, E Bridie ; Sullivan, Lucy ; Kyparissoudis, Konstantinos ; Kjer-Nielsen, Lars ; Vivian, Julian ; Cao, Benjamin ; Brooks, Andrew ; Williams, Spencer ; Illarionov, Petr ; Besra, Gurdyal ; Turner, Stephen ; Porcelli, Steven ; McCluskey, James ; Smyth, Mark ; Rossjohn, Jamie ; Godfrey, Dale. / A semi-invariant V{alpha}10{+} T cell antigen receptor defines a population of natural killer T cells with distinct glycolipid antigen-recognition properties. In: Nature Immunology. 2011 ; Vol. 12, No. 7. pp. 616 - 623.
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title = "A semi-invariant V{alpha}10{+} T cell antigen receptor defines a population of natural killer T cells with distinct glycolipid antigen-recognition properties",
abstract = "Type I natural killer T cells (NKT cells) are characterized by an invariant variable region 14-joining region 18 (V(alpha)14-J(alpha)18) T cell antigen receptor (TCR) alpha-chain and recognition of the glycolipid alpha-galactosylceramide (alpha-GalCer) restricted to the antigen-presenting molecule CD1d. Here we describe a population of alpha-GalCer-reactive NKT cells that expressed a canonical V(alpha)10-J(alpha)50 TCR alpha-chain, which showed a preference for alpha-glucosylceramide (alpha-GlcCer) and bacterial alpha-glucuronic acid-containing glycolipid antigens. Structurally, despite very limited TCRalpha sequence identity, the V(alpha)10 TCR-CD1d-alpha-GlcCer complex had a docking mode similar to that of type I TCR-CD1d-alpha-GalCer complexes, although differences at the antigen-binding interface accounted for the altered antigen specificity. Our findings provide new insight into the structural basis and evolution of glycolipid antigen recognition and have notable implications for the scope and immunological role of glycolipid-specific T cell responses.",
author = "Adam Uldrich and Onisha Patel and Garth Cameron and Daniel Pellicci and Day, {E Bridie} and Lucy Sullivan and Konstantinos Kyparissoudis and Lars Kjer-Nielsen and Julian Vivian and Benjamin Cao and Andrew Brooks and Spencer Williams and Petr Illarionov and Gurdyal Besra and Stephen Turner and Steven Porcelli and James McCluskey and Mark Smyth and Jamie Rossjohn and Dale Godfrey",
year = "2011",
doi = "10.1038/ni.2051",
language = "English",
volume = "12",
pages = "616 -- 623",
journal = "Nature Immunology",
issn = "1529-2908",
publisher = "Nature Publishing Group",
number = "7",

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Uldrich, A, Patel, O, Cameron, G, Pellicci, D, Day, EB, Sullivan, L, Kyparissoudis, K, Kjer-Nielsen, L, Vivian, J, Cao, B, Brooks, A, Williams, S, Illarionov, P, Besra, G, Turner, S, Porcelli, S, McCluskey, J, Smyth, M, Rossjohn, J & Godfrey, D 2011, 'A semi-invariant V{alpha}10{+} T cell antigen receptor defines a population of natural killer T cells with distinct glycolipid antigen-recognition properties' Nature Immunology, vol. 12, no. 7, pp. 616 - 623. https://doi.org/10.1038/ni.2051

A semi-invariant V{alpha}10{+} T cell antigen receptor defines a population of natural killer T cells with distinct glycolipid antigen-recognition properties. / Uldrich, Adam; Patel, Onisha; Cameron, Garth; Pellicci, Daniel; Day, E Bridie; Sullivan, Lucy; Kyparissoudis, Konstantinos; Kjer-Nielsen, Lars; Vivian, Julian; Cao, Benjamin; Brooks, Andrew; Williams, Spencer; Illarionov, Petr; Besra, Gurdyal; Turner, Stephen; Porcelli, Steven; McCluskey, James; Smyth, Mark; Rossjohn, Jamie; Godfrey, Dale.

In: Nature Immunology, Vol. 12, No. 7, 2011, p. 616 - 623.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - A semi-invariant V{alpha}10{+} T cell antigen receptor defines a population of natural killer T cells with distinct glycolipid antigen-recognition properties

AU - Uldrich, Adam

AU - Patel, Onisha

AU - Cameron, Garth

AU - Pellicci, Daniel

AU - Day, E Bridie

AU - Sullivan, Lucy

AU - Kyparissoudis, Konstantinos

AU - Kjer-Nielsen, Lars

AU - Vivian, Julian

AU - Cao, Benjamin

AU - Brooks, Andrew

AU - Williams, Spencer

AU - Illarionov, Petr

AU - Besra, Gurdyal

AU - Turner, Stephen

AU - Porcelli, Steven

AU - McCluskey, James

AU - Smyth, Mark

AU - Rossjohn, Jamie

AU - Godfrey, Dale

PY - 2011

Y1 - 2011

N2 - Type I natural killer T cells (NKT cells) are characterized by an invariant variable region 14-joining region 18 (V(alpha)14-J(alpha)18) T cell antigen receptor (TCR) alpha-chain and recognition of the glycolipid alpha-galactosylceramide (alpha-GalCer) restricted to the antigen-presenting molecule CD1d. Here we describe a population of alpha-GalCer-reactive NKT cells that expressed a canonical V(alpha)10-J(alpha)50 TCR alpha-chain, which showed a preference for alpha-glucosylceramide (alpha-GlcCer) and bacterial alpha-glucuronic acid-containing glycolipid antigens. Structurally, despite very limited TCRalpha sequence identity, the V(alpha)10 TCR-CD1d-alpha-GlcCer complex had a docking mode similar to that of type I TCR-CD1d-alpha-GalCer complexes, although differences at the antigen-binding interface accounted for the altered antigen specificity. Our findings provide new insight into the structural basis and evolution of glycolipid antigen recognition and have notable implications for the scope and immunological role of glycolipid-specific T cell responses.

AB - Type I natural killer T cells (NKT cells) are characterized by an invariant variable region 14-joining region 18 (V(alpha)14-J(alpha)18) T cell antigen receptor (TCR) alpha-chain and recognition of the glycolipid alpha-galactosylceramide (alpha-GalCer) restricted to the antigen-presenting molecule CD1d. Here we describe a population of alpha-GalCer-reactive NKT cells that expressed a canonical V(alpha)10-J(alpha)50 TCR alpha-chain, which showed a preference for alpha-glucosylceramide (alpha-GlcCer) and bacterial alpha-glucuronic acid-containing glycolipid antigens. Structurally, despite very limited TCRalpha sequence identity, the V(alpha)10 TCR-CD1d-alpha-GlcCer complex had a docking mode similar to that of type I TCR-CD1d-alpha-GalCer complexes, although differences at the antigen-binding interface accounted for the altered antigen specificity. Our findings provide new insight into the structural basis and evolution of glycolipid antigen recognition and have notable implications for the scope and immunological role of glycolipid-specific T cell responses.

UR - http://www.nature.com/ni/journal/v12/n7/pdf/ni.2051.pdf

U2 - 10.1038/ni.2051

DO - 10.1038/ni.2051

M3 - Article

VL - 12

SP - 616

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JO - Nature Immunology

JF - Nature Immunology

SN - 1529-2908

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