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Updated: Jul 5, 2026

Interview: Glycolipid Antigen Presentation by CD1d and the Therapeutic Potential of NKT cell Activation
18:08

Interview: Glycolipid Antigen Presentation by CD1d and the Therapeutic Potential of NKT cell Activation

Published on: December 31, 2007

Cutting edge: nonglycosidic CD1d lipid ligands activate human and murine invariant NKT cells

Jonathan D Silk1, Mariolina Salio, B Gopal Reddy

  • 1Tumour Immunology Group, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, Oxford, UK.

Journal of Immunology (Baltimore, Md. : 1950)
|May 6, 2008
PubMed

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 alpha-galactosylceramide-pulsed DCs due to the weaker affinity of the human iNKT TCR for CD1d/ threitolceramide than CD1d/alpha-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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