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

Pellicci DG, Clarke AJ, Patel O, Mallevaey T, Beddoe T, Le Nours J, Uldrich AP, McCluskey J, Besra GS, Porcelli SA, Gapin L, Godfrey DI, Rossjohn J
Nat Immunol 12 827-33 (2011)
Related entries: 3scm, 3sda, 3sdc, 3sdx

Cited: 95 times
EuropePMC logo PMID: 21804559

Abstract

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.

Reviews - 3sdd mentioned but not cited (1)

  1. Recognition of CD1d-restricted antigens by natural killer T cells. Rossjohn J, Pellicci DG, Patel O, Gapin L, Godfrey DI. Nat Rev Immunol 12 845-857 (2012)

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Reviews citing this publication (38)

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