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Abstract
The CD1 family is a large cluster of non-polymorphic, major histocompatibility complex (MHC) class-I-like molecules that bind distinct lipid-based antigens that are recognized by T cells. The most studied group of T cells that interact with lipid antigens are natural killer T (NKT) cells, which characteristically express a semi-invariant T-cell receptor ( NKT TCR) that specifically recognizes the CD1 family member, CD1d. NKT-cell-mediated recognition of the CD1d - antigen complex has been implicated in microbial immunity, tumour immunity, autoimmunity and allergy. Here we describe the structure of a human NKT TCR in complex with CD1d bound to the potent NKT-cell agonist alpha-galactosylceramide, the archetypal CD1d-restricted glycolipid. In contrast to T-cell receptor - peptide- antigen - MHC complexes, the NKT TCR docked parallel to, and at the extreme end of the CD1d-binding cleft, which enables a lock-and-key type interaction with the lipid antigen. The structure provides a basis for the interaction between the highly conserved NKT TCR alpha-chain and the CD1d - antigen complex that is typified in innate immunity, and also indicates how variability of the NKT TCR beta-chain can impact on recognition of other CD1d - antigen complexes. These findings provide direct insight into how a T-cell receptor recognizes a lipid-antigen-presenting molecule of the immune system.
Original language | English |
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Pages (from-to) | 44-49 |
Number of pages | 6 |
Journal | Nature |
Volume | 448 |
Issue number | 7149 |
Early online date | 20 Jun 2007 |
DOIs | |
Publication status | Published - 20 Jun 2007 |
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Dive into the research topics of 'CD1d–lipid-antigen recognition by the semi-invariant NKT T-cell receptor'. Together they form a unique fingerprint.Projects
- 1 Finished
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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