Glycolipids that elicit IFN-?-biased responses from natural killer T cells.

ABSTRACT: Natural killer T (NKT) cells recognize glycolipids presented by CD1d. The first antigen described, ?-galactosyl ceramide (?GalCer), is a potential anticancer agent whose activity depends upon IFN-? secretion. We report two analogs of ?GalCer based on a naturally occurring glycosphingolipid, plakoside A. These compounds induce enhanced IFN-? that correlates with detergent-resistant binding to CD1d and an increased stability of the lipid-CD1d complexes on antigen-presenting cells. Structural analysis on one of the analogs indicates that it is more deeply bound inside the CD1d groove, suggesting tighter lipid-CD1d interactions. To our knowledge, this is the first example in which structural information provides an explanation for the increased lipid-CD1d stability, likely responsible for the Th1 bias. We provide insights into the mechanism of IFN-?-inducing compounds, and because our compounds activate human NKT cells, they could have therapeutic utility.

SUBMITTER: Tyznik AJ 

PROVIDER: S-EPMC3246403 | biostudies-literature | 2011 Dec

REPOSITORIES: biostudies-literature