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Non-glycosidic compounds can stimulate both human and mouse iNKT cells.


ABSTRACT: Invariant natural killer T (iNKT) cells recognize CD1d/glycolipid complexes and upon activation with synthetic agonists display immunostimulatory properties. We have previously described that the non-glycosidic CD1d-binding lipid, threitolceramide (ThrCer) activates murine and human iNKT cells. Here, we show that incorporating the headgroup of ThrCer into a conformationally more restricted 6- or 7-membered ring results in significantly more potent non-glycosidic analogs. In particular, ThrCer 6 was found to promote strong anti-tumor responses and to induce a more prolonged stimulation of iNKT cells than does the canonical ?-galactosylceramide (?-GalCer), achieving an enhanced T-cell response at lower concentrations compared with ?-GalCer both in vitro, using human iNKT-cell lines and in vivo, using C57BL/6 mice. Collectively, these studies describe novel non-glycosidic ThrCer-based analogs that have improved potency in iNKT-cell activation compared with that of ?-GalCer, and are clinically relevant iNKT-cell agonists.

SUBMITTER: Jukes JP 

PROVIDER: S-EPMC4913735 | biostudies-literature | 2016 May

REPOSITORIES: biostudies-literature

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Non-glycosidic compounds can stimulate both human and mouse iNKT cells.

Jukes John-Paul JP   Gileadi Uzi U   Ghadbane Hemza H   Yu Ting-Fong TF   Shepherd Dawn D   Cox Liam R LR   Besra Gurdyal S GS   Cerundolo Vincenzo V  

European journal of immunology 20160301 5


Invariant natural killer T (iNKT) cells recognize CD1d/glycolipid complexes and upon activation with synthetic agonists display immunostimulatory properties. We have previously described that the non-glycosidic CD1d-binding lipid, threitolceramide (ThrCer) activates murine and human iNKT cells. Here, we show that incorporating the headgroup of ThrCer into a conformationally more restricted 6- or 7-membered ring results in significantly more potent non-glycosidic analogs. In particular, ThrCer 6  ...[more]

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