Adaptability of the semi-invariant natural killer T-cell receptor towards structurally diverse CD1d-restricted ligands

Sebastian Joyce, William C. Florence, Chengfeng Xia, Laura E. Gordy, Wenlan Chen, Yalong Zhang, James Scott-Browne, Yuki Kinjo, Karl O.A. Yu, Santosh Keshipeddy, Daniel G. Pellicci, Onisha Patel, Lars Kjer-Nielsen, James McCluskey, Dale I. Godfrey, Jamie Rossjohn, Stewart K. Richardson, Steven A. Porcelli, Amy R. Howell, Kyoko HayakawaLaurent Gapin, Dirk M. Zajonc, Peng George Wang

Research output: Contribution to journalArticle

36 Scopus citations

Abstract

The semi-invariant natural killer (NK) T-cell receptor (NKTcr) recognises structurally diverse glycolipid antigens presented by the monomorphic CD1d molecule. While the α-chain of the NKTcr is invariant, the Β-chain is more diverse, but how this diversity enables the NKTcr to recognise diverse antigens, such as an α-linked monosaccharide (α-galactosylceramide and α-galactosyldiacylglycerol) and the Β-linked trisaccharide (isoglobotriaosylceramide), is unclear. We demonstrate here that NKTcrs, which varied in their Β-chain usage, recognised diverse glycolipid antigens with a similar binding mode on CD1d. Nevertheless, the NKTcrs recognised distinct epitopic sites within these antigens, including α-galactosylceramide, the structurally similar α-galactosyldiacylglycerol and the very distinct isoglobotriaosylceramide. We also show that the relative roles of the CDR loops within the NKTcr Β-chain varied as a function of the antigen. Thus, while NKTcrs characteristically use a conserved docking mode, the NKTcr Β-chain allows these cells to recognise unique aspects of structurally diverse CD1d-restricted ligands.

Original languageEnglish (US)
Pages (from-to)3579-3590
Number of pages12
JournalEMBO Journal
Volume28
Issue number22
DOIs
StatePublished - Nov 2009

Keywords

  • Antigen recognition
  • Glycolipid antigens
  • NKT cells
  • Recognition logic
  • Semi-invariant T-cell receptor

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

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    Joyce, S., Florence, W. C., Xia, C., Gordy, L. E., Chen, W., Zhang, Y., Scott-Browne, J., Kinjo, Y., Yu, K. O. A., Keshipeddy, S., Pellicci, D. G., Patel, O., Kjer-Nielsen, L., McCluskey, J., Godfrey, D. I., Rossjohn, J., Richardson, S. K., Porcelli, S. A., Howell, A. R., ... Wang, P. G. (2009). Adaptability of the semi-invariant natural killer T-cell receptor towards structurally diverse CD1d-restricted ligands. EMBO Journal, 28(22), 3579-3590. https://doi.org/10.1038/emboj.2009.286