文摘
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Summary
Natural killer T (NKT) cells recognize glycolipids presented by CD1d. The first antigen described, ¦Á-galactosyl ceramide (¦ÁGalCer), is a potential anticancer agent whose activity depends upon IFN-¦Ã secretion. We report two analogs of ¦ÁGalCer based on a naturally occurring glycosphingolipid, plakoside A. These compounds induce enhanced IFN-¦Ã 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-¦Ã-inducing compounds, and because our compounds activate human NKT cells, they could have therapeutic utility.