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

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

doi:10.1038/ni.2051

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

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

Microbiology & Immunology

Research output: Contribution to journal › Article › peer-review

94 Scopus citations

Abstract

Type I natural killer T cells (NKT cells) are characterized by an invariant variable region 14-joining region 18 (V_α 14-J _α 18) T cell antigen receptor (TCR) _α-chain and recognition of the glycolipid α-galactosylceramide (α-GalCer) restricted to the antigen-presenting molecule CD1d. Here we describe a population of α-GalCer-reactive NKT cells that expressed a canonical V_α 10-J_α 50 TCR_α-chain, which showed a preference for α-glucosylceramide (α-GlcCer) and bacterial α-glucuronic acid-containing glycolipid antigens. Structurally, despite very limited TCRα sequence identity, the V_α 10 TCR-CD1d-α-GlcCer complex had a docking mode similar to that of type I TCR-CD1d-α-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 language	English (US)
Pages (from-to)	616-623
Number of pages	8
Journal	Nature Immunology
Volume	12
Issue number	7
DOIs	https://doi.org/10.1038/ni.2051
State	Published - May 2011

ASJC Scopus subject areas

Immunology and Allergy
Immunology

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Uldrich, A. P., Patel, O., Cameron, G., Pellicci, D. G., Day, E. B., Sullivan, L. C., Kyparissoudis, K., Kjer-Nielsen, L., Vivian, J. P., Cao, B., Brooks, A. G., Williams, S. J., Illarionov, P., Besra, G. S., Turner, S. J., Porcelli, S. A., McCluskey, J., Smyth, M. J., Rossjohn, J., & Godfrey, D. I. (2011). A semi-invariant V_α 10⁺ T cell antigen receptor defines a population of natural killer T cells with distinct glycolipid antigen-recognition properties. Nature Immunology, 12(7), 616-623. https://doi.org/10.1038/ni.2051

Uldrich, AP, Patel, O, Cameron, G, Pellicci, DG, Day, EB, Sullivan, LC, Kyparissoudis, K, Kjer-Nielsen, L, Vivian, JP, Cao, B, Brooks, AG, Williams, SJ, Illarionov, P, Besra, GS, Turner, SJ, Porcelli, SA, McCluskey, J, Smyth, MJ, Rossjohn, J & Godfrey, DI 2011, 'A semi-invariant V_α 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

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title = "A semi-invariant Vα 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 (Vα 14-J α 18) T cell antigen receptor (TCR) α-chain and recognition of the glycolipid α-galactosylceramide (α-GalCer) restricted to the antigen-presenting molecule CD1d. Here we describe a population of α-GalCer-reactive NKT cells that expressed a canonical Vα 10-Jα 50 TCRα-chain, which showed a preference for α-glucosylceramide (α-GlcCer) and bacterial α-glucuronic acid-containing glycolipid antigens. Structurally, despite very limited TCRα sequence identity, the Vα 10 TCR-CD1d-α-GlcCer complex had a docking mode similar to that of type I TCR-CD1d-α-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.",

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AU - Sullivan, Lucy C.

AU - Kyparissoudis, Konstantinos

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AU - Brooks, Andrew G.

AU - Williams, Spencer J.

AU - Illarionov, Petr

AU - Besra, Gurdyal S.

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AU - Porcelli, Steven A.

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AU - Smyth, Mark J.

AU - Rossjohn, Jamie

AU - Godfrey, Dale I.

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

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