STRUCTURE-ACTIVITY RELATIONSHIP AND CONFORMATIONAL-ANALYSIS OF MONOGLYCOSYLCERAMIDES ON THE SYNGENEIC MIXED LEUKOCYTE REACTION

We examined effects of alpha-, beta-galactosylceramides (CalCers) and alpha-, beta-glucosylceramides (GlcCers) on the syngeneic mixed leukoc yte reaction (MLR) using spleen cells (responder cells) and dendritic cells (DC, stimulator cells). The DC pretreated with these alpha-monog lycosylceramides markedly stimulated the proliferation of spleen cells , in contrast to the little stimulatory effects produced by the DC pre treated with the corresponding beta-anomers. In addition, when we comp ared the effects of alpha-GalCer derivatives on the syngeneic MLR, it appeared that the 2 ''- and 3-hydroxyl groups in alpha-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 c ommon to alpha-GalCer and alpha-GlcCer are not accessible to those of inactive monoglycosyleeramides such as beta-GalCer. These results sugg est that there might be a receptor-like site for alpha-monoglycosylcer amides on the cells which are involved in the MLR response. (C) 1998 E lsevier Science Ltd. All rights reserved.