4ZAK

Crystal structure of the mCD1d/DB06-1/iNKTCR ternary complex

Summary for 4ZAK

• Entry DOI: 10.2210/pdb4zak/pdb
• Descriptor: Antigen-presenting glycoprotein CD1d1, Beta-2-microglobulin, Protein Trav11,Va14Ja18/Vb8.2,Human nkt tcr alpha chain, ... (7 entities in total)
• Functional Keywords: mhc-fold, ig-fold, glycolipid antigen presentation, t cell receptor, immune system
• Biological source: Mus musculus (Mouse); More
• Total number of polymer chains: 4
• Total formula weight: 96116.84

Authors

Zajonc, D.M.,Birkholz, A.M. (deposition date: 2015-04-13, release date: 2015-07-01, Last modification date: 2024-10-09)

Primary citation

Birkholz, A.M.,Girardi, E.,Wingender, G.,Khurana, A.,Wang, J.,Zhao, M.,Zahner, S.,Illarionov, P.A.,Wen, X.,Li, M.,Yuan, W.,Porcelli, S.A.,Besra, G.S.,Zajonc, D.M.,Kronenberg, M.
A Novel Glycolipid Antigen for NKT Cells That Preferentially Induces IFN-gamma Production.
J Immunol., 195:924-933, 2015

PubMed 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.

PubMed: 26078271
DOI: 10.4049/jimmunol.1500070

Experimental method

X-RAY DIFFRACTION (2.824 Å)