Glycolipid α-C-galactosylceramide is a distinct inducer of dendritic cell function during innate and adaptive immune responses of mice

Publisher Website
Google Scholar
Abstract
α-Galactosylceramide (α-GalCer) is the prototype compound for studying the presentation of glycolipids on CD1d molecules to natural killer T (NKT) lymphocytes. A single i.v. dose of glycolipid triggers a cascade of events involving the production of several cytokines over the course of a day, a short-lived activation of NKT and natural killer (NK) cells, and a more prolonged adaptive T cell immune response if certain antigens are given together with α-GalCer. We find that a recently described analogue, α-C-galactosylceramide (α-C-GalCer), more potently induces these innate and adaptive immune responses in mice. α-C-GalCer acts as a more effective trigger for IL-12 and IFN-γ production, although it minimally elicits IL-4 and TNF-α release into the serum. Also, α-C-GalCer better mobilizes NKT and natural killer cells to resist B16 melanoma. To help understand these effects, we find that α-C-GalCer binds more stably to dendritic cells than α-GalCer and that dendritic cells loaded with α-C-GalCer induce larger and more long lasting NKT cell responses in vivo . When glycolipid is targeted to dendritic cells in spleen together with antigens in dying cells, such as irradiated tumor cells, α-C-GalCer is active as an adjuvant for T cell-mediated immunity at lower doses, just 20 ng per mouse, where it is also able to up-regulate the required CD40L costimulatory molecule on NKT cells. Therefore, α-C-GalCer represents a glycolipid that binds more stably to dendritic cells and acts as a more effective link between innate and adaptive immunity in vivo .