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Recognition of β-linked self glycolipids mediated by natural killer T cell antigen receptors.
- Source :
-
Nature immunology [Nat Immunol] 2011 Jul 31; Vol. 12 (9), pp. 827-33. Date of Electronic Publication: 2011 Jul 31. - Publication Year :
- 2011
-
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.
- Subjects :
- Amino Acid Sequence
Animals
Antigens, CD1d chemistry
Antigens, CD1d metabolism
Binding Sites
Crystallography, X-Ray
Flow Cytometry
Galactosylceramides chemistry
Galactosylceramides metabolism
Globosides chemistry
Globosides metabolism
Humans
Hybridomas
Kinetics
Mice
Models, Molecular
Molecular Mimicry
Molecular Sequence Data
Natural Killer T-Cells cytology
Natural Killer T-Cells metabolism
Protein Binding immunology
Protein Engineering methods
Structure-Activity Relationship
Surface Plasmon Resonance
Trihexosylceramides chemistry
Trihexosylceramides metabolism
Antigens, CD1d immunology
Autoimmunity
Galactosylceramides immunology
Globosides immunology
Natural Killer T-Cells immunology
Receptors, Antigen, T-Cell, alpha-beta chemistry
Receptors, Antigen, T-Cell, alpha-beta immunology
Receptors, Antigen, T-Cell, alpha-beta metabolism
Trihexosylceramides immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1529-2916
- Volume :
- 12
- Issue :
- 9
- Database :
- MEDLINE
- Journal :
- Nature immunology
- Publication Type :
- Academic Journal
- Accession number :
- 21804559
- Full Text :
- https://doi.org/10.1038/ni.2076