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Publication Abstract from PubMed

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

Glycolipids that Elicit IFN-gamma-Biased Responses from Natural Killer T Cells.,Tyznik AJ, Farber E, Girardi E, Birkholz A, Li Y, Chitale S, So R, Arora P, Khurana A, Wang J, Porcelli SA, Zajonc DM, Kronenberg M, Howell AR Chem Biol. 2011 Dec 23;18(12):1620-30. PMID:22195564^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.