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PDBsum entry 4zak
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Immune system
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PDB id
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4zak
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Contents |
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267 a.a.
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98 a.a.
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203 a.a.
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239 a.a.
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References listed in PDB file
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Key reference
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Title
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A novel glycolipid antigen for nkt cells that preferentially induces ifn-γ Production.
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Authors
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A.M.Birkholz,
E.Girardi,
G.Wingender,
A.Khurana,
J.Wang,
M.Zhao,
S.Zahner,
P.A.Illarionov,
X.Wen,
M.Li,
W.Yuan,
S.A.Porcelli,
G.S.Besra,
D.M.Zajonc,
M.Kronenberg.
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Ref.
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J Immunol, 2015,
195,
924-933.
[DOI no: ]
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PubMed id
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Abstract
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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.
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