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Recognition of β-linked self glycolipids mediated by natural killer T cell antigen receptors

Pellicci, Daniel G., Clarke, Andrew J., Patel, Onisha, Mallevaey, Thierry, Beddoe, Travis, Le Nours, Jérôme, Uldrich, Adam P., McCluskey, James, Besra, Gurdyal S., Porcelli, Steven A., Gapin, Laurent, Godfrey, Dale I. and Rossjohn, Jamie 2011. Recognition of β-linked self glycolipids mediated by natural killer T cell antigen receptors. Nature Immunology 12 (9) , pp. 827-833. 10.1038/ni.2076

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The most potent foreign antigens for natural killer T cells (NKT cells) are α-linked glycolipids, whereas NKT cell self-reactivity involves weaker recognition of structurally distinct β-linked glycolipid antigens. Here we provide the mechanism for the autoreactivity of T cell antigen receptors (TCRs) on NKT cells to the mono- and tri-glycosylated β-linked agonists β-galactosylceramide (β-GalCer) and isoglobotrihexosylceramide (iGb3), respectively. In binding these disparate antigens, the NKT cell TCRs docked onto CD1d similarly, achieving this by flattening the conformation of the β-linked ligands regardless of the size of the glycosyl head group. Unexpectedly, the antigenicity of iGb3 was attributable to its terminal sugar group making compensatory interactions with CD1d. Thus, the NKT cell TCR molds the β-linked self ligands to resemble the conformation of foreign α-linked ligands, which shows that induced-fit molecular mimicry can underpin the self-reactivity of NKT cell TCRs to β-linked antigens.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Systems Immunity Research Institute (SIURI)
Subjects: Q Science > QH Natural history > QH301 Biology
Q Science > QR Microbiology > QR180 Immunology
Publisher: Nature Publishing Group
ISSN: 1529-2908
Last Modified: 04 Jun 2017 05:06

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