Implications for invariant natural killer T cell ligands due to the restricted presence of isoglobotrihexosylceramide in mammals

Anneliese O. Speak, Mariolina Salio, David C A Neville, Josette Fontaine, David A. Priestman, Nick Platt, Tanya Heare, Terry D. Butters, Raymond A. Dwek, Francois Trottein, Mark A. Exley, Vincenzo Cerundolo, Frances M. Platt

    Research output: Contribution to journalArticlepeer-review

    Abstract

    Development of invariant natural killer T (iNKT) cells requires the presentation of lipid ligand(s) by CD1d molecules in the thymus. The glycosphingolipid (GSL) isoglobotrihexosylceramide (iGb3) has been proposed as the natural iNKT cell-selecting ligand in the thymus and to be involved in peripheral activation of iNKT cells by dendritic cells (DCs). However, there is no direct biochemical evidence for the presence of iGb3 in mouse or human thymus or DCs. Using a highly sensitive HPLC assay, the only tissue where iGb3 could be detected in mouse was the dorsal root ganglion (DRG). iGb3 was not detected in other mouse or any human tissues analyzed, including thymus and DCs. Even in mutant mice that store isoglobo-series GSLs in the DRG, we were still unable to detect these GSLs in the thymus. iGb3 is therefore unlikely to be a physiologically relevant iNKT cell-selecting ligand in mouse and humans. A detailed study is now warranted to better understand the nature of iNKT cell-selecting ligand(s) in vivo. © 2007 by The National Academy of Sciences of the USA.
    Original languageEnglish
    Pages (from-to)5971-5976
    Number of pages5
    JournalProceedings of the National Academy of Sciences of the United States of America
    Volume104
    Issue number14
    DOIs
    Publication statusPublished - 3 Apr 2007

    Keywords

    • CD1d
    • Glycosphingolipid
    • Lipid presentation
    • Thymus

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