PMID: 17581592

 

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Title : CD1d-lipid-antigen recognition by the semi-invariant NKT T-cell receptor

Abstract :

1. 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
2. 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
3. NK T-cell-mediated recognition of the CD1d-antigen complex has been implicated in microbial immunity, tumour immunity, autoimmunity and allergy
4. Here we describe the structure of a human NKT TCR in complex with CD1d bound to the potent NK T-cell agonist alpha-galactosylceramide, the archetypal CD1d-restricted glycolipid
5. 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
6. 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
7. These findings provide direct insight into how a T-cell receptor recognizes a lipid-antigen-presenting molecule of the immune system