Modification of the Ceramide Moiety of Isoglobotrihexosylceramide on Its Agonist Activity in Stimulation of Invariant Natural Killer T Cells

摘要

Isoglobotrihexosylceramide (iGb3) is an endogenous antigen of mammalian cells and can stimulate invariant natural killer T (iNKT) cells to evoke autoimmune activities by the release of T helper 1 (Thl) and Th2 cytokines. Thl cytokines are correlated with the antitumor and antiviral response, while Th2 cytokines are correlated with the amelioration of autoimmune diseases. iGb3 is a very weak agonist compared to the exogenous a-galactosylceramide; however, modification of the ceramide moiety has been advocated as one of the approaches to improve its stimulatory activity and to change the bias of release of Thl and Th2 cytokines. Two analogues of iGb3,2H-iGb3 and HO-iGb3 with different ceramide moieties, were synthesized. Bioassay results showed that HO-iGb3 was much more effective in stimulating iNKT cells than iGb3 at low concentration. The assay also showed that the CDld/2H-iGb3 complexes are remarkably efficient in stimulating iNKT cells.