Journal article

Antigen Specificity of Type I NKT Cells Is Governed by TCR beta-Chain Diversity

Garth Cameron, Daniel G Pellicci, Adam P Uldrich, Gurdyal S Besra, Petr Illarionov, Spencer J Williams, Nicole L La Gruta, Jamie Rossjohn, Dale I Godfrey

JOURNAL OF IMMUNOLOGY | AMER ASSOC IMMUNOLOGISTS | Published : 2015

Abstract

NKT cells recognize lipid-based Ags presented by CD1d. Type I NKT cells are often referred to as invariant owing to their mostly invariant TCR α-chain usage (Vα14-Jα18 in mice, Vα24-Jα18 in humans). However, these cells have diverse TCR β-chains, including Vβ8, Vβ7, and Vβ2 in mice and Vβ11 in humans, joined to a range of TCR Dβ and Jβ genes. In this study, we demonstrate that TCR β-chain composition can dramatically influence lipid Ag recognition in an Ag-dependent manner. Namely, the glycolipids α-glucosylceramide and isoglobotrihexosylceramide were preferentially recognized by Vβ7(+) NKT cells from mice, whereas the α-galactosylceramide analog OCH, with a truncated sphingosine chain, was ..

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Grants

Awarded by National Health and Medical Research Council of Australia


Awarded by National Health and Medical Research Council of Australia Biomedical Fellowship


Awarded by Australian Research Council Future Fellowship


Awarded by National Health and Medical Research Council of Australia Senior Principal Research Fellowship


Awarded by National Health and Medical Research Council of Australia Fellowship


Awarded by Medical Research Council


Funding Acknowledgements

This work was supported by National Health and Medical Research Council of Australia Grants 1013667, 1021972, 5671222, and 1046333 and by program and project grants from the Cancer Council Victoria. G.C. was supported by a Cancer Research Institute predoctoral fellowship. D.G.P. is supported by National Health and Medical Research Council of Australia Biomedical Fellowship 1054431; A.P.U. is supported by Australian Research Council Future Fellowship FT140100278; N.L.L.G. is supported by a Sylvia and Charles Viertel Foundation senior medical research fellowship; D.I.G. is supported by National Health and Medical Research Council of Australia Senior Principal Research Fellowship 1020770; and J.R. is supported by National Health and Medical Research Council of Australia Fellowship AF50.