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Immunology. 2009 Jun;127(2):216-225. doi: 10.1111/j.1365-2567.2008.02943.x.

Identification of C-glycoside analogues that display a potent biological activity against murine and human invariant natural killer T cells.

Author information

1
Aaron Diamond AIDS Research Center, The Rockefeller University, NY 10016, USA.

Abstract

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.

PMID:
19489127
PMCID:
PMC2691787
DOI:
10.1111/j.1365-2567.2008.02943.x
[Indexed for MEDLINE]
Free PMC Article

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