Journal
JOURNAL OF IMMUNOLOGY
Volume 180, Issue 10, Pages 6452-6456Publisher
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.180.10.6452
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Funding
- MRC [G9900061, MC_U137884181, G0501975] Funding Source: UKRI
- Medical Research Council [G0501975, MC_U137884181, G9900061] Funding Source: researchfish
- Cancer Research UK [C375, C399/A2291] Funding Source: Medline
- Medical Research Council [G9900061, G0501975, MC_U137884181] Funding Source: Medline
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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 energy. 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 cell agonists. The ability of these compounds to assist the priming of Ag-specific immune responses while minimizing iNKT cell-dependent DC is makes them attractive adjuvants for vaccination strategies.
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