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Abstract
In this article, we characterize a novel Ag for invariant NKT (iNKT) cells capable of producing an especially robust Th1 response. This glycosphingolipid, DB06-1, is similar in chemical structure to the well-studied α-galactosylceramide (αGalCer), with the only change being a single atom: the substitution of a carbonyl oxygen with a sulfur atom. Although DB06-1 is not a more effective Ag in vitro, the small chemical change has a marked impact on the ability of this lipid Ag to stimulate iNKT cells in vivo, with increased IFN-γ production at 24 h compared with αGalCer, increased IL-12, and increased activation of NK cells to produce IFN-γ. These changes are correlated with an enhanced ability of DB06-1 to load in the CD1d molecules expressed by dendritic cells in vivo. Moreover, structural studies suggest a tighter fit into the CD1d binding groove by DB06-1 compared with αGalCer. Surprisingly, when iNKT cells previously exposed to DB06-1 are restimulated weeks later, they have greatly increased IL-10 production. Therefore, our data are consistent with a model whereby augmented and or prolonged presentation of a glycolipid Ag leads to increased activation of NK cells and a Th1-skewed immune response, which may result, in part, from enhanced loading into CD1d. Furthermore, our data suggest that strong antigenic stimulation in vivo may lead to the expansion of IL-10-producing iNKT cells, which could counteract the benefits of increased early IFN-γ production.
Original language | English |
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Journal | Journal of Immunology |
DOIs | |
Publication status | Published - 15 Jun 2015 |
Bibliographical note
Copyright © 2015 by The American Association of Immunologists, Inc.Fingerprint
Dive into the research topics of 'A Novel Glycolipid Antigen for NKT Cells That Preferentially Induces IFN-γ Production'. Together they form a unique fingerprint.Projects
- 1 Finished
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Design, synthesis, and assessment of specific iNKT cell agonists for clinical applications
Besra, D., Cox, L., Cunningham, A. & Lammas, T.
1/03/12 → 29/02/16
Project: Research Councils