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Cutting Edge : Nonglycosidic CD1d Lipid Ligands Activate Human and Murine Invariant NKT Cells

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2008

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Silk, Jonathan D.
Salio, Mariolina
Reddy, B. Gopal
Shepherd, Dawn
Gileadi, Uzi
Brown, James
Masri, S. Hajar
Polzella, Paolo
Cerundolo, Vincenzo
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https://doi.org/10.4049/jimmunol.180.10.6452
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The Journal of Immunology. American Association of Immunologists. 2008, 180(10), pp. 6452-6456. ISSN 0022-1767. eISSN 1550-6606. Available under: doi: 10.4049/jimmunol.180.10.6452

Zusammenfassung

Invariant NKT cells (iNKT cells) recognize CD1d/glycolipid complexes. We demonstrate that the nonglycosidic compound threitolceramide efficiently activates iNKT cells, resulting in dendritic cell (DC) maturation and the priming of Ag-specific T and B cells. Threitolceramide-pulsed DCs are more resistant to iNKT cell-dependent lysis than α-galactosylceramide-pulsed DCs due to the weaker affinity of the human iNKT TCR for CD1d/ threitolceramide than CD1d/α-galactosylceramide complexes. iNKT cells stimulated with threitolceramide also recover more quickly from activation-induced anergy. Kinetic and functional experiments showed that shortening or lengthening the threitol moiety by one hydroxymethylene group modulates ligand recognition, as human and murine iNKT cells recognize glycerolceramide and arabinitolceramide differentially. Our data broaden the range of potential iNKT cell agonists. The ability of these compounds to assist the priming of Ag-specific immune responses while minimizing iNKT cell-dependent DC lysis makes them attractive adjuvants for vaccination strategies.

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ISO 690SILK, Jonathan D., Mariolina SALIO, B. Gopal REDDY, Dawn SHEPHERD, Uzi GILEADI, James BROWN, S. Hajar MASRI, Paolo POLZELLA, Richard R. SCHMIDT, Vincenzo CERUNDOLO, 2008. Cutting Edge : Nonglycosidic CD1d Lipid Ligands Activate Human and Murine Invariant NKT Cells. In: The Journal of Immunology. American Association of Immunologists. 2008, 180(10), pp. 6452-6456. ISSN 0022-1767. eISSN 1550-6606. Available under: doi: 10.4049/jimmunol.180.10.6452
BibTex
@article{Silk2008Cutti-58690,
  year={2008},
  doi={10.4049/jimmunol.180.10.6452},
  title={Cutting Edge : Nonglycosidic CD1d Lipid Ligands Activate Human and Murine Invariant NKT Cells},
  number={10},
  volume={180},
  issn={0022-1767},
  journal={The Journal of Immunology},
  pages={6452--6456},
  author={Silk, Jonathan D. and Salio, Mariolina and Reddy, B. Gopal and Shepherd, Dawn and Gileadi, Uzi and Brown, James and Masri, S. Hajar and Polzella, Paolo and Schmidt, Richard R. and Cerundolo, Vincenzo}
}
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