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

Research output: Contribution to journalArticle

81 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)616-623
Number of pages8
JournalNature Immunology
Volume12
Issue number7
DOIs
StatePublished - May 1 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 Vα 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