| First Author | Birkholz AM | Year | 2015 |
| Journal | J Immunol | Volume | 195 |
| Issue | 3 | Pages | 924-33 |
| PubMed ID | 26078271 | Mgi Jnum | J:242806 |
| Mgi Id | MGI:5906547 | Doi | 10.4049/jimmunol.1500070 |
| Citation | Birkholz AM, et al. (2015) A Novel Glycolipid Antigen for NKT Cells That Preferentially Induces IFN-gamma Production. J Immunol 195(3):924-33 |
| abstractText | 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 alpha-galactosylceramide (alphaGalCer), 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-gamma production at 24 h compared with alphaGalCer, increased IL-12, and increased activation of NK cells to produce IFN-gamma. 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 alphaGalCer. 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-gamma production. |
