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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.
Original language | English |
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Pages (from-to) | 827-33 |
Number of pages | 7 |
Journal | Nature Immunology |
Volume | 12 |
Issue number | 9 |
DOIs | |
Publication status | Published - 1 Sept 2011 |
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Dive into the research topics of 'Recognition of β-linked self glycolipids mediated by natural killer T cell antigen receptors'. Together they form a unique fingerprint.Projects
- 2 Finished
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Design, synthesis, and assessment of specific iNKT cell agonists for clinical applications
Besra, D., Cox, L., Cunningham, A. & Lammas, T.
1/03/12 → 29/02/16
Project: Research Councils
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Modulation of Immune Responses by aGalCer Analogues Through Differential Activation of CD1d-restricted NKT Cells
Besra, D. & Lammas, T.
1/06/05 → 30/11/09
Project: Research Councils