NKT TCR recognition of CD1d-α-C-galactosylceramide

Onisha Patel, Garth Cameron, Daniel G. Pellicci, Zheng Liu, Hoe Sup Byun, Travis Beddoe, James McCluskey, Richard W. Franck, A. Raúl Castaño, Youssef Harrak, Amadeu Llebaria, Robert Bittman, Steven A. Porcelli, Dale I. Godfrey, Jamie Rossjohn

Research output: Contribution to journalArticle

42 Scopus citations

Abstract

NKT cells respond to a variety of CD1d-restricted glycolipid Ags that are structurally related to the prototypic Ag α-galactosylceramide (α-GalCer). A modified analog of α-GalCer with a carbon-based glycosidic linkage (α-C-GalCer) has generated great interest because of its apparent ability to promote prolonged, Th1-biased immune responses. In this study, we report the activation of spleen NKT cells to α-C-GalCer, and related C-glycoside ligands, is weaker than that of α-GalCer. Furthermore, the Vβ8.2 and Vβ7 NKT TCR affinity for CD1d-&al[pha;-C-GalCer, and some related analogs, is ∼10-fold lower than that for the NKT TCR-CD1d-α- GalCer interaction. Nevertheless, the crystal structure of the Vβ8.2 NKT TCR-CD1d-α-C-GalCer complex is similar to that of the corresponding NKT TCR-CD1d-α-GalCer complex, although subtle differences at the interface provide a basis for understanding the lower affinity of the NKT TCR-CD1d-α-C-GalCer interaction. Our findings support the concept that for CD1d-restricted NKT cells, altered glycolipid ligands can promote markedly different responses while adopting similar TCR-docking topologies.

Original languageEnglish (US)
Pages (from-to)4705-4713
Number of pages9
JournalJournal of Immunology
Volume187
Issue number9
DOIs
StatePublished - Nov 1 2011

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ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Patel, O., Cameron, G., Pellicci, D. G., Liu, Z., Byun, H. S., Beddoe, T., McCluskey, J., Franck, R. W., Castaño, A. R., Harrak, Y., Llebaria, A., Bittman, R., Porcelli, S. A., Godfrey, D. I., & Rossjohn, J. (2011). NKT TCR recognition of CD1d-α-C-galactosylceramide. Journal of Immunology, 187(9), 4705-4713. https://doi.org/10.4049/jimmunol.1100794