Involvement of secretory and endosomal compartments in presentation of an exogenous self-glycolipid to type II NKT cells.
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.
Roy
Keshab Chandra
KC
Laboratory of Autoimmunity, Torrey Pines Institute for Molecular Studies, San Diego, CA 92121, USA.
Maricic
Igor
I
Khurana
Archana
A
Smith
Trevor R F
TR
Halder
Ramesh C
RC
Kumar
Vipin
V
D000818:Animals; D017951:Antigen Presentation / Q000276:immunology*; D018949:Antigens, CD1 / Q000276:immunology / Q000378:metabolism; D055610:Antigens, CD1d; D001324:Autoantigens / Q000276:immunology / Q000378:metabolism; D011992:Endosomes / Q000276:immunology / Q000378:metabolism*; D018984:Epitopes, T-Lymphocyte / Q000276:immunology / Q000378:metabolism; D005260:Female; D005699:Galactosylceramides / Q000276:immunology* / Q000378:metabolism; D006825:Hybridomas; D007694:Killer Cells, Natural / Q000145:classification / Q000276:immunology* / Q000378:metabolism; D008024:Ligands; D051379:Mice; D008810:Mice, Inbred C57BL; D022142:Secretory Vesicles / Q000276:immunology / Q000378:metabolism*; D013433:Sulfoglycosphingolipids / Q000276:immunology* / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000145:classification / Q000276:immunology* / Q000378:metabolism
D018949:Antigens, CD1; D055610:Antigens, CD1d; D001324:Autoantigens; D018984:Epitopes, T-Lymphocyte; D005699:Galactosylceramides; D008024:Ligands; D013433:Sulfoglycosphingolipids