Sulfatide inhibits α-galactosylceramide presentation by dendritic cells

Sulfatide-reactive type II NKT cells, the so-called non-invariant NKT (non-iNKT) cells, have been shown to counteract invariant NKT (iNKT) cell activity. However, the effects of sulfatide on activation of iNKT cells by alpha-galactocylceramide (alpha GC) in the context of CD1d have not been studied in detail. Therefore, we studied the blocking effect of sulfatide on alpha GC-induced iNKT cell activation by dendritic cells (DCs). Even in the absence of non-iNKT cells, sulfatide inhibited alpha GC-mediated iNKT cell activation by reducing alpha GC/CD1d complex formations in a dose-dependent manner. This was also confirmed in a cell-free setting using immobilized CD1d-Ig. Moreover, simultaneous injection of alpha GC with sulfatide decreased alpha GC/CD1d complex formations on DCs, accompanied by the reduced CD40L-up-regulation and IFN-gamma production by iNKT cells and IL-12p70 production by DCs. However, sulfatide by itself did not interfere with the presentation of MHC class II-mediated antigen presentation to specific T cells. These results demonstrate that sulfatide competes with alpha GC to be loaded onto CD1d along the endocytic pathway in DCs, thereby inhibiting the iNKT cell response.