Involvement of Secretory and Endosomal Compartments in Presentation of an Exogenous Self-Glycolipid to Type II NKT Cells

Laboratory of Autoimmunity, Torrey Pines Institute for Molecular Studies, San Diego, CA 92121, USA.
The Journal of Immunology (Impact Factor: 4.92). 04/2008; 180(5):2942-50. DOI: 10.4049/jimmunol.180.5.2942
Source: PubMed


Natural Killer T (NKT) cells recognize both self and foreign lipid Ags presented by CD1 molecules. Although presentation of the marine sponge-derived lipid alphaGalCer to type I NKT cells has been well studied, little is known about self-glycolipid presentation to either type I or type II NKT cells. Here we have investigated presentation of the self-glycolipid sulfatide to a type II NKT cell that specifically recognizes a single species of sulfatide, namely lyso-sulfatide but not other sulfatides containing additional acyl chains. In comparison to other sulfatides or alphaGalCer, lyso-sulfatide binds with lower affinity to CD1d. Although plate-bound CD1d is inefficient in presenting lyso-sulfatide at neutral pH, it is efficiently presented at acidic pH and in the presence of saposin C. The lysosomal trafficking of mCD1d is required for alphaGalCer presentation to type I NKT cells, it is not important for presentation of lyso-sulfatide to type II NKT cells. Consistently, APCs deficient in a lysosomal lipid-transfer protein effectively present lyso-sulfatide. Presentation of lyso-sulfatide is inhibited in the presence of primaquine, concanamycin A, monensin, cycloheximide, and an inhibitor of microsomal triglyceride transfer protein but remains unchanged following treatment with brefeldin A. Wortmannin-mediated inhibition of lipid presentation indicates an important role for the PI-3kinase in mCD1d trafficking. Our data collectively suggest that weak CD1d-binding self-glycolipid ligands such as lyso-sulfatide can be presented via the secretory and endosomal compartments. Thus this study provides important insights into the exogenous self-glycolipid presentation to CD1d-restricted T cells.

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    • "We investigated whether intracellular vesicle transport in the T cell is essential for LFA-1-mediated migration. Primaquine (PQ) is a lysosomotrophic amine that slows recycling by blocking membrane fusion of exocytic vesicles and has been used to assess a requirement for vesicular recycling in various T cell activities (Pathak and Blum, 2000; Reid and Watts, 1990; Roberts et al., 2002; Roy et al., 2008). Following 5 min pre-treatment with PQ, both the random migration and average speed of HSB2 T cells were normal at 40 mM, reduced by 40% at 100 mM and by 70% at 300 mM PQ with no impact on cell viability (Fig. 1A). "
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