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PDBsum entry 3qux
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Immune system
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PDB id
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3qux
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Contents |
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266 a.a.
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96 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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Galactose-Modified inkt cell agonists stabilized by an induced fit of cd1d prevent tumour metastasis.
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Authors
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S.Aspeslagh,
Y.Li,
E.D.Yu,
N.Pauwels,
M.Trappeniers,
E.Girardi,
T.Decruy,
K.Van beneden,
K.Venken,
M.Drennan,
L.Leybaert,
J.Wang,
R.W.Franck,
S.Van calenbergh,
D.M.Zajonc,
D.Elewaut.
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Ref.
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EMBO J, 2011,
30,
2294-2305.
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PubMed id
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Abstract
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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 α-galactosylceramide structurally related glycolipids with marked
Th1 bias in both mice and men, leading to superior tumour protection in vivo.
The strength of the Th1 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, α-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.
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