Syntheses of biotinylated alpha-galactosylceramides and their effects on the immune system and CD1 molecules.
A representative alpha-galactosylceramide (alpha-GalCer), KRN7000, has strong immunostimulatory and antitumor activity. Recent studies demonstrated that KRN7000-pulsed antigen-presenting cells (APC) can activate natural killer T (NKT) cells, a novel T-cell lineage, and CD1d molecules on APC play an important role in the activation of NKT cells. However, it remains unclear whether alpha-GalCers actually bind to CD1d molecules. To address this question, we synthesized three kinds of biotinylated alpha-GalCer and a biotinylated beta-GalCer and found that the biotinylated alpha-GalCers significantly stimulate the proliferation of murine spleen cells, but the biotinylated beta-GalCer does not and that all biotinylated compounds bind to CD1d molecules.
Sakai
T
T
Pharmaceutical Research Laboratory, Kirin Brewery Company, Ltd., 3 Miyahara-cho, Takasaki-shi, Gunma 370-1295, Japan.
Naidenko
O V
OV
Iijima
H
H
Kronenberg
M
M
Koezuka
Y
Y
D000818:Animals; D018949:Antigens, CD1 / Q000378:metabolism*; D055610:Antigens, CD1d; D019921:Biotinylation; D002455:Cell Division / Q000187:drug effects; D005699:Galactosylceramides / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D011485:Protein Binding; D013154:Spleen / Q000166:cytology / Q000187:drug effects; D013329:Structure-Activity Relationship; D020349:Surface Plasmon Resonance
D018949:Antigens, CD1; D055610:Antigens, CD1d; C526877:CD1D protein, human; D005699:Galactosylceramides