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

• Published in: The Journal of immunology (1950) Vol. 180; no. 5; pp. 2942 - 2950
• Main Authors: Roy, Keshab Chandra, Maricic, Igor, Khurana, Archana, Smith, Trevor R. F, Halder, Ramesh C, Kumar, Vipin
• Format: Journal Article
• Language: English
• Published: United States Am Assoc Immnol 01-03-2008
• Subjects: Animals; Antigen Presentation - immunology; Antigens, CD1 - immunology; Antigens, CD1 - metabolism; Antigens, CD1d; Autoantigens - immunology; Autoantigens - metabolism; Endosomes - immunology; Endosomes - metabolism; Epitopes, T-Lymphocyte - immunology; Epitopes, T-Lymphocyte - metabolism; Female; Galactosylceramides - immunology; Galactosylceramides - metabolism; Hybridomas; Killer Cells, Natural - classification; Killer Cells, Natural - immunology; Killer Cells, Natural - metabolism; Ligands; Mice; Mice, Inbred C57BL; Secretory Vesicles - immunology; Secretory Vesicles - metabolism; Sulfoglycosphingolipids - immunology; Sulfoglycosphingolipids - metabolism; T-Lymphocyte Subsets - classification; T-Lymphocyte Subsets - immunology; T-Lymphocyte Subsets - metabolism
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.180.5.2942

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.