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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.

Original publication




Journal article


Journal of immunology (Baltimore, Md. : 1950)

Publication Date





6452 - 6456


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


Dendritic Cells, Killer Cells, Natural, T-Lymphocyte Subsets, T-Lymphocytes, Animals, Humans, Mice, Sugar Alcohols, Ceramides, Galactosylceramides, Antigens, CD1, Adjuvants, Immunologic, Ligands, Enzyme-Linked Immunosorbent Assay, Flow Cytometry, Surface Plasmon Resonance, Lymphocyte Activation, Antigen Presentation, Protein Binding, Models, Molecular, Antigens, CD1d