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Identification of C‐glycoside analogues that display a potent biological activity against murine and human invariant natural killer T cells
Author(s) -
Li Xiangming,
Chen Guangwu,
GarciaNavarro Raquel,
Franck Richard W.,
Tsuji Moriya
Publication year - 2009
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1111/j.1365-2567.2008.02943.x
Subject(s) - in vitro , glycolipid , biological activity , glycoside , natural killer t cell , biology , natural killer cell , biochemistry , chemistry , stereochemistry , cytotoxic t cell
Summary We have recently shown that α‐C‐galactosylceramide (α‐C‐GalCer) stimulates invariant natural killer T (iNKT) cells and preferentially induces a T helper 1 (Th1)‐type response in mice. However, α‐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 α‐galactosylceramide (α‐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.