期刊
EMBO JOURNAL
卷 30, 期 11, 页码 2294-2305出版社
WILEY
DOI: 10.1038/emboj.2011.145
关键词
CD1d; glycolipids; iNKT cells
资金
- Cancer Research Institute
- NIH [RO1 AI074952]
- FWO Flanders
- Belgian Stichting tegen Kanker
Invariant natural killer T (iNKT) cells are known to have marked immunomodulatory capacity due to their ability to produce copious amounts of effector cytokines. Here, we report the structure and function of a novel class of aromatic alpha-galactosylceramide structurally related glycolipids with marked Th1 bias in both mice and men, leading to superior tumour protection in vivo. The strength of the Thl response correlates well with enhanced lipid binding to CD1d as a result of an induced fit mechanism that binds the aromatic substitution as a third anchor, in addition to the two lipid chains. This induced fit is in contrast to another Th1-biasing glycolipid, alpha-C-GalCer, whose CD1d binding follows a conventional key-lock principle. These findings highlight the previously unexploited flexibility of CD1d in accommodating galactose-modified glycolipids and broaden the range of glycolipids that can stimulate iNKT cells. We speculate that glycolipids can be designed that induce a similar fit, thereby leading to superior and more sustained iNKT cell responses in vivo. The EMBO Journal (2011) 30, 2294-2305. doi:10.1038/emboj.2011.145; Published online 6 May 2011
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