CD1d–lipid-antigen recognition by the semi-invariant NKT T-cell receptor
| Autor: | Ruide Koh, Kwok Soon Wun, James McCluskey, Gurdyal S. Besra, Mandvi Bharadwaj, Dale I. Godfrey, Natalie A. Borg, Daniel G. Pellicci, Jamie Rossjohn, Matthew C.J. Wilce, Lars Kjer-Nielsen |
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| Rok vydání: | 2007 |
| Předmět: |
Protein Conformation
Receptors Antigen T-Cell alpha-beta T-Lymphocytes T cell Antigen presentation CD1 Galactosylceramides chemical and pharmacologic phenomena Biology Crystallography X-Ray Major histocompatibility complex Antigens CD1 Mice Immune system Species Specificity Antigen T-Lymphocyte Subsets Carbohydrate Conformation medicine Animals Humans Antigen Presentation Multidisciplinary T-cell receptor hemic and immune systems Killer Cells Natural medicine.anatomical_structure CD1D Immunology biology.protein lipids (amino acids peptides and proteins) Antigens CD1d |
| Zdroj: | Nature. 448:44-49 |
| ISSN: | 1476-4687 0028-0836 |
| DOI: | 10.1038/nature05907 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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