TY - JOUR
T1 - NKT TCR recognition of CD1d-a-C-galactosylceramide
AU - Patel, Onisha
AU - Cameron, Garth
AU - Pellicci, Daniel
AU - Liu, Zheng
AU - Byun, Hoe-Sup
AU - Beddoe, Travis
AU - McCluskey, James
AU - Franck, Richard
AU - Castano, A
AU - Harrak, Youssef
AU - Llebaria, Amadeu
AU - Bittman, Robert
AU - Porcelli, Steven
AU - Godfrey, Dale
AU - Rossjohn, Jamie
PY - 2011
Y1 - 2011
N2 - NKT cells respond to a variety of CD1d-restricted glycolipid Ags that are structurally related to the prototypic Ag alpha-galactosylceramide (alpha-GalCer). A modified analog of alpha-GalCer with a carbon-based glycosidic linkage (alpha-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 alpha-C-GalCer, and related C-glycoside ligands, is weaker than that of alpha-GalCer. Furthermore, the Vbeta8.2 and Vbeta7 NKT TCR affinity for CD1d-alpha-C-GalCer, and some related analogs, is approximately 10-fold lower than that for the NKT TCR-CD1d-alpha-GalCer interaction. Nevertheless, the crystal structure of the Vbeta8.2 NKT TCR-CD1d-alpha-C-GalCer complex is similar to that of the corresponding NKT TCR-CD1d-alpha-GalCer complex, although subtle differences at the interface provide a basis for understanding the lower affinity of the NKT TCR-CD1d-alpha-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.
AB - NKT cells respond to a variety of CD1d-restricted glycolipid Ags that are structurally related to the prototypic Ag alpha-galactosylceramide (alpha-GalCer). A modified analog of alpha-GalCer with a carbon-based glycosidic linkage (alpha-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 alpha-C-GalCer, and related C-glycoside ligands, is weaker than that of alpha-GalCer. Furthermore, the Vbeta8.2 and Vbeta7 NKT TCR affinity for CD1d-alpha-C-GalCer, and some related analogs, is approximately 10-fold lower than that for the NKT TCR-CD1d-alpha-GalCer interaction. Nevertheless, the crystal structure of the Vbeta8.2 NKT TCR-CD1d-alpha-C-GalCer complex is similar to that of the corresponding NKT TCR-CD1d-alpha-GalCer complex, although subtle differences at the interface provide a basis for understanding the lower affinity of the NKT TCR-CD1d-alpha-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.
UR - http://www.jimmunol.org/content/187/9/4705.full.pdf+html
U2 - 10.4049/jimmunol.1100794
DO - 10.4049/jimmunol.1100794
M3 - Article
SN - 0022-1767
VL - 187
SP - 4705
EP - 4713
JO - Journal of Immunology
JF - Journal of Immunology
IS - 9
ER -