NKT TCR Recognition of CD1d-α-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, Onisha
  • Cameron, Garth
  • Pellicci, Daniel G
  • Liu, Zheng
  • Byun, Hoe-Sup
  • Beddoe, Travis
  • McCluskey, James
  • Franck, Richard W
  • Castaño, A Raúl
  • Harrak, Youssef
  • Llebaria, Amadeu
  • Bittman, Robert
  • Porcelli, Steven A
  • Godfrey, Dale I
  • Rossjohn, Jamie

publication date

  • November 1, 2011