Cutting edge: Nonglycosidic CD1d lipid ligands activate human and murine invariant NKT cells Journal Article
| Authors: | Silk, J. D.; Salio, M.; Reddy, B. G.; Shepherd, D.; Gileadi, U.; Brown, J.; Masri, S. H.; Polzella, P.; Ritter, G.; Besra, G. S.; Jones, E. Y.; Schmidt, R. R.; Cerundolo, V. |
| Article Title: | Cutting edge: Nonglycosidic CD1d lipid ligands activate human and murine invariant NKT cells |
| Abstract: | Invariant NKT cells (iNKT cells) recognize CD1dlglyco-lipid 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 CDld/threitolceramide than CDld/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 hydroxymethy-lene 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 minimizmg iNKT cell-dependent DC lysis makes them attractive adjuvants for vaccination strategies. Copyright © 2008 by The American Association of Immunologists, Inc. |
| Keywords: | unclassified drug; human cell; nonhuman; flow cytometry; t lymphocyte; t-lymphocytes; animal cell; mouse; animal; metabolism; animals; mice; cell maturation; dendritic cell; animal experiment; protein binding; enzyme linked immunosorbent assay; b lymphocyte; antigen presentation; immunology; lymphocyte activation; dendritic cells; chemistry; molecular recognition; ligand; ligands; natural killer cell; killer cells, natural; immunological adjuvant; models, molecular; chemical structure; t-lymphocyte subsets; enzyme-linked immunosorbent assay; adjuvants, immunologic; surface plasmon resonance; cell activation; t lymphocyte subpopulation; synthesis; ceramide; ceramides; alpha galactosylceramide; cd1d antigen; natural killer t cell; galactosylceramide; glycolipid; cd1 antigen; antigens, cd1; alpha-galactosylceramide; galactosylceramides; threitolceramide; sugar alcohol; threitol; invariant natural killer t cell; sugar alcohols |
| Journal Title: | Journal of Immunology |
| Volume: | 180 |
| Issue: | 10 |
| ISSN: | 0022-1767 |
| Publisher: | The American Association of Immunologists, Inc |
| Date Published: | 2008-05-15 |
| Start Page: | 6452 |
| End Page: | 6456 |
| Language: | English |
| PUBMED: | 18453560 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 35" - "Export Date: 17 November 2011" - "CODEN: JOIMA" - "Source: Scopus" |
