title: Binding and antigen presentation of ceramide-containing glycolipids by soluble mouse and human CD1d molecules.
abstract: We have purified soluble mouse and human CD1d molecules to assess the structural requirements for lipid antigen presentation by CD1. Plate-bound CD1d molecules from either species can present the glycolipid alpha-galactosyl ceramide (alpha-GalCer) to mouse natural killer T cells, formally demonstrating both the in vitro formation of antigenic complexes, and the presentation of alpha-GalCer by these two CD1d molecules. Using surface plasmon resonance, we show that at neutral pH, mouse CD1 and human CD1d bind to immobilized alpha-GalCer, unlike human CD1b, which requires acidic pH for lipid antigen binding. The CD1d molecules can also bind both to the nonantigenic beta-GalCer and to phosphatidylethanolamine, indicating that diverse lipids can bind to CD1d. These studies provide the first quantitative analysis of monomeric lipid antigen-CD1 interactions, and they demonstrate that the orientation of the galactose, or even the nature of the polar head group, are likely to be more important for T cell receptor contact than CD1d binding.
authors.affiliation: Department of Microbiology and Immunology and the Molecular Biology Institute, University of California at Los Angeles, Los Angeles, California 90095, USA.
authors.forename: O V
authors.initials: OV
authors.lastname: Naidenko
authors.forename: J K
authors.initials: JK
authors.lastname: Maher
authors.forename: W A
authors.initials: WA
authors.lastname: Ernst
authors.forename: T
authors.initials: T
authors.lastname: Sakai
authors.forename: R L
authors.initials: RL
authors.lastname: Modlin
authors.forename: M
authors.initials: M
authors.lastname: Kronenberg
mesh_terms: D000818:Animals; D017951:Antigen Presentation / Q000276:immunology*; D018949:Antigens, CD1 / Q000276:immunology*; D055610:Antigens, CD1d; D001667:Binding, Competitive; D019921:Biotinylation; D002518:Ceramides / Q000276:immunology*; D006017:Glycolipids / Q000276:immunology*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007694:Killer Cells, Natural / Q000276:immunology; D007700:Kinetics; D051379:Mice; D010714:Phosphatidylethanolamines / Q000276:immunology; D011485:Protein Binding; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D011994:Recombinant Proteins / Q000276:immunology; D012995:Solubility; D020349:Surface Plasmon Resonance; D001613:beta 2-Microglobulin / Q000235:genetics / Q000276:immunology
chemical_list: D018949:Antigens, CD1; D055610:Antigens, CD1d; C526877:CD1D protein, human; D002518:Ceramides; D006017:Glycolipids; D010714:Phosphatidylethanolamines; D011948:Receptors, Antigen, T-Cell; D011994:Recombinant Proteins; D001613:beta 2-Microglobulin