| Literature DB >> 22195564 |
Aaron J Tyznik1, Elisa Farber, Enrico Girardi, Alysia Birkholz, Yali Li, Sampada Chitale, Regina So, Pooja Arora, Archana Khurana, Jing Wang, Steven A Porcelli, Dirk M Zajonc, Mitchell Kronenberg, Amy R Howell.
Abstract
Natural killer T (NKT) cells recognize glycolipids presented by CD1d. The first antigen described, α-galactosyl ceramide (αGalCer), is a potential anticancer agent whose activity depends upon IFN-γ secretion. We report two analogs of αGalCer based on a naturally occurring glycosphingolipid, plakoside A. These compounds induce enhanced IFN-γ 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-γ-inducing compounds, and because our compounds activate human NKT cells, they could have therapeutic utility.Entities:
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Year: 2011 PMID： 22195564 PMCID： PMC3246403 DOI： 10.1016/j.chembiol.2011.10.015
Source DB: PubMed Journal: Chem Biol ISSN： 1074-5521