Abstract
We examined effects of α-, β-galactosylceramides (CalCers) and α-, β-glucosylceramides (GlcCers) on the syngeneic mixed leukocyte reaction (MLR) using spleen cells (responder cells) and dendritic cells (DC, stimulator cells). The DC pretreated with these α-monoglycosylceramides markedly stimulated the proliferation of spleen cells, in contrast to the little stimulatory effects produced by the DC pretreated with the corresponding β-anomers. In addition, when we compared the effects of α-GalCer derivatives on the syngeneic MLR, it appeared that the 2″- and 3-hydroxyl groups in α-GalCers play a critical role in their stimulation of the MLR response. Based on these results, we performed a computer-aided molecular modeling study, and found that the orientations of the 2″-, 4″- and 3-hydroxyl groups common to α-GalCer and α-GlcCer are not accessible to those of inactive monoglycosyleeramides such as β-GalCer. These results suggest that there might be a receptor-like site for α-monoglycosylceramides on the cells which are involved in the MLR response.
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