NKT TCR Recognition of CD1d- -C-Galactosylceramide Academic Article uri icon

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-α-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.

authors

  • Patel, O
  • Cameron, G
  • Pellicci, DG
  • Liu, Z
  • Byun, H.-S
  • Beddoe, T
  • McCluskey, J
  • Franck, RW
  • Castano, AR
  • Harrak, Y
  • Llebaria, A
  • Bittman, R
  • Porcelli, SA
  • Godfrey, DI
  • Rossjohn, J

publication date

  • November 1, 2011