Identification of C-glycoside analogues that display a potent  biological activity against murine and human invariant natural  killer T cells.
We have recently shown that alpha-C-galactosylceramide (alpha-C-GalCer) stimulates invariant natural killer T (iNKT) cells and preferentially induces a T helper 1 (Th1)-type response in mice. However, alpha-C-GalCer was found to be a rather weak ligand against human iNKT cells in vitro. Therefore, in this study, we sought to identify a compound that displays a strong stimulatory activity against human iNKT cells, by determining the biological activities of several C-glycoside analogues. From the in vitro screening assays, we found that almost all C-glycoside analogues, which have an E-alkene linker between sugar and lipid moieties, are able to activate human iNKT cells and to induce the maturation and activation of human dendritic cells through iNKT-cell activation. In summary, although alpha-galactosylceramide (alpha-GalCer) remains the strongest iNKT-cell ligand, our study identified E-alkene-linked C-glycoside analogues as potent human iNKT-cell stimulants, and indicated that these analogues could be used as a therapeutic agent in the future for diseases resolved by Th1-type responses.
Li
Xiangming
X
Aaron Diamond AIDS Research Center, The Rockefeller University, NY 10016, USA.
Chen
Guangwu
G
Garcia-Navarro
Raquel
R
Franck
Richard W
RW
Tsuji
Moriya
M
D000328:Adult; D000368:Aged; D000818:Animals; D017951:Antigen Presentation / Q000276:immunology; D055610:Antigens, CD1d / Q000032:analysis; D002454:Cell Differentiation / Q000276:immunology; D002460:Cell Line; D016207:Cytokines / Q000096:biosynthesis; D003713:Dendritic Cells / Q000276:immunology; D005260:Female; D006017:Glycolipids / Q000276:immunology; D006027:Glycosides; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008875:Middle Aged; D009005:Monosaccharides / Q000494:pharmacology*; D055611:Natural Killer T-Cells / Q000187:drug effects* / Q000276:immunology; D013154:Spleen / Q000276:immunology; D018417:Th1 Cells; D055815:Young Adult
D055610:Antigens, CD1d; C438934:C-glycoside; C526879:Cd1d1 protein, mouse; D016207:Cytokines; D006017:Glycolipids; D006027:Glycosides; D009005:Monosaccharides; D007371:Interferon-gamma