A Novel Glycolipid Antigen for NKT Cells That Preferentially Induces IFN-γ Production

摘要: In this article, we characterize a novel Ag for invariant NKT (iNKT) cells capable of producing an especially robust Th1 response. This glycosphingolipid, DB06-1, is similar in chemical structure to the well-studied α-galactosylceramide (αGalCer), with only change being single atom: substitution carbonyl oxygen sulfur atom. Although DB06-1 not more effective vitro, small has marked impact on ability lipid stimulate iNKT vivo, increased IFN-γ production at 24 h compared αGalCer, IL-12, and activation NK produce IFN-γ. These changes are correlated enhanced load CD1d molecules expressed by dendritic vivo. Moreover, structural studies suggest tighter fit into binding groove αGalCer. Surprisingly, when previously exposed restimulated weeks later, they have greatly IL-10 production. Therefore, our data consistent model whereby augmented or prolonged presentation glycolipid leads Th1-skewed immune response, which may result, part, from loading CD1d. Furthermore, that strong antigenic stimulation vivo lead expansion IL-10–producing cells, could counteract benefits early