Saposins modulate human invariant Natural Killer T cells self-reactivity and facilitate lipid exchange with CD1d molecules during antigen presentation
Abstract
Understanding how to optimize lipid-loading onto CD1d molecules is important to better harness invariant natural killer T (iNKT) cells' central role at the interface between innate and adaptive immunity. We report that the lipid transfer proteins saposins play an essential role in modulating human iNKT cell autoreactivity to antigen-presenting cells activated by inflammatory stimuli. Lipid-loading occurs in an endo-lysosomal compartment, where saposins work as "lipid editors," capable of fine-tuning loading and unloading of CD1d molecules and increasing the off-rate of CD1d-bound lipids.
- Publication:
-
Proceedings of the National Academy of Science
- Pub Date:
- December 2013
- DOI:
- 10.1073/pnas.1310050110
- Bibcode:
- 2013PNAS..110E4753S