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Lysosomal recycling terminates CD1d-mediated presentation of short and polyunsaturated variants of the NKT cell lipid antigen αGalCer.
- Source :
-
Proceedings of the National Academy of Sciences of the United States of America . 6/23/2009, Vol. 106 Issue 25, p10254-10259. 6p. 5 Graphs. - Publication Year :
- 2009
-
Abstract
- Short or polyunsaturated lipid variants of the NKT cell antigen a-galactosylceramide (sGC) exhibit decreased potency and a Th2 bias in vivo despite conserved TCR contact residues and stable binding to CD1d at neutral and acidic pH. Using reagents to directly visualize lipids in their free or CD1d-bound form, we determined that, contrary to predictions, these lipids reached the lysosome better than αGC. However, in contrast with αGC, they loaded CD1 d at the cell surface and underwent immediate pH-dependent dissociation upon recycling to the lysosome. In cell-free assays, ultrafast dissociation of preformed complexes could be induced at acidic pH only when free competitor lipids were added, suggesting active lipid displacement. These findings provide a common cell biological explanation for the decreased stimulatory properties of short and polyunsaturated αGC variants. They also suggest that direct lipid displacement is a potent mechanism underlying highly dynamic lipid exchange reactions in the lysosomal compartment that shape the repertoire of lipids associated with CD1d. [ABSTRACT FROM AUTHOR]
- Subjects :
- *CD antigens
*LIPIDS
*PH effect
*LYSOSOMES
*KILLER cells
*T cells
*EXCHANGE reactions
Subjects
Details
- Language :
- English
- ISSN :
- 00278424
- Volume :
- 106
- Issue :
- 25
- Database :
- Academic Search Index
- Journal :
- Proceedings of the National Academy of Sciences of the United States of America
- Publication Type :
- Academic Journal
- Accession number :
- 43244654
- Full Text :
- https://doi.org/10.1073/pnas.0901228106