Implications for invariant natural killer T cell ligands due to the restricted presence of isoglobotrihexosylceramide in mammals.
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.
Speak
Anneliese O
AO
Department of Pharmacology, University of Oxford, Mansfield Road, Oxford OX1 3QT, United Kingdom.
Salio
Mariolina
M
Neville
David C A
DC
Fontaine
Josette
J
Priestman
David A
DA
Platt
Nick
N
Heare
Tanya
T
Butters
Terry D
TD
Dwek
Raymond A
RA
Trottein
Francois
F
Exley
Mark A
MA
Cerundolo
Vincenzo
V
Platt
Frances M
FM
D000818:Animals; D018949:Antigens, CD1 / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D003713:Dendritic Cells; D005727:Ganglia, Spinal / Q000378:metabolism; D005915:Globosides / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D007694:Killer Cells, Natural / Q000166:cytology / Q000276:immunology*; D008024:Ligands; D008322:Mammals / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008817:Mice, Mutant Strains; D013950:Thymus Gland
D018949:Antigens, CD1; D005915:Globosides; D008024:Ligands; C037097:isoglobotriaosylceramide