Abstract
NKT cells respond to a variety of CD1d-restricted glycolipid Ags that are structurally related to the prototypic Ag α-galactosylceramide (α-GalCer). A modified analog of α-GalCer with a carbon-based glycosidic linkage (α-C-GalCer) has generated great interest because of its apparent ability to promote prolonged, Th1-biased immune responses. In this study, we report the activation of spleen NKT cells to α-C-GalCer, and related C-glycoside ligands, is weaker than that of α-GalCer. Furthermore, the Vβ8.2 and Vβ7 NKT TCR affinity for CD1d-&al[pha;-C-GalCer, and some related analogs, is ∼10-fold lower than that for the NKT TCR-CD1d-α- GalCer interaction. Nevertheless, the crystal structure of the Vβ8.2 NKT TCR-CD1d-α-C-GalCer complex is similar to that of the corresponding NKT TCR-CD1d-α-GalCer complex, although subtle differences at the interface provide a basis for understanding the lower affinity of the NKT TCR-CD1d-α-C-GalCer interaction. Our findings support the concept that for CD1d-restricted NKT cells, altered glycolipid ligands can promote markedly different responses while adopting similar TCR-docking topologies.
Original language | English (US) |
---|---|
Pages (from-to) | 4705-4713 |
Number of pages | 9 |
Journal | Journal of Immunology |
Volume | 187 |
Issue number | 9 |
DOIs | |
State | Published - Nov 1 2011 |
ASJC Scopus subject areas
- Immunology and Allergy
- Immunology