title: Saposin C is required for lipid presentation by human CD1b.
abstract: Lipids from Mycobacterium tuberculosis are presented through CD1 proteins to T lymphocytes in humans, but the accessory molecules required for antigen loading and presentation remain unidentified. Here we show that fibroblasts deficient in sphingolipid activator proteins (SAPs) transfected with CD1b failed to activate lipid-specific T cells. However, the T cell response was restored when fibroblasts were reconstituted with SAP-C but not other SAPs. Lipid antigen and SAP-C colocalized in lysosomal compartments, and liposome assays showed that SAP-C efficiently extracts antigen from membranes. Coprecipitation demonstrated direct molecular interaction between SAP-C and CD1b. We propose a model in which SAP-C exposes lipid antigens from intralysosomal membranes for loading onto CD1b. Thus, SAP-C represents a missing link in antigen presentation of lipids through CD1b to human T cells.
authors.affiliation: Max-Planck-Institute for Infection Biology, Department of Immunology, Schumannstrasse 21-22, D-10117 Berlin, Germany.
authors.forename: Florian
authors.initials: F
authors.lastname: Winau
authors.forename: Vera
authors.initials: V
authors.lastname: Schwierzeck
authors.forename: Robert
authors.initials: R
authors.lastname: Hurwitz
authors.forename: Natascha
authors.initials: N
authors.lastname: Remmel
authors.forename: Peter A
authors.initials: PA
authors.lastname: Sieling
authors.forename: Robert L
authors.initials: RL
authors.lastname: Modlin
authors.forename: Steven A
authors.initials: SA
authors.lastname: Porcelli
authors.forename: Volker
authors.initials: V
authors.lastname: Brinkmann
authors.forename: Masahiko
authors.initials: M
authors.lastname: Sugita
authors.forename: Konrad
authors.initials: K
authors.lastname: Sandhoff
authors.forename: Stefan H E
authors.initials: SH
authors.lastname: Kaufmann
authors.forename: Ulrich E
authors.initials: UE
authors.lastname: Schaible
mesh_terms: D017951:Antigen Presentation; D000938:Antigen-Presenting Cells / Q000276:immunology / Q000378:metabolism; D018949:Antigens, CD1 / Q000378:metabolism*; D005347:Fibroblasts / Q000276:immunology / Q000378:metabolism; D006023:Glycoproteins / Q000172:deficiency / Q000235:genetics / Q000276:immunology*; D006801:Humans; D066298:In Vitro Techniques; D008055:Lipids / Q000276:immunology*; D008213:Lymphocyte Activation; D008247:Lysosomes / Q000276:immunology / Q000378:metabolism; D011485:Protein Binding; D049231:Saposins; D049128:Sphingolipid Activator Proteins; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D014162:Transfection; D001617:beta-Glucosidase / Q000378:metabolism
chemical_list: D018949:Antigens, CD1; C419394:CD1b antigen; D006023:Glycoproteins; D008055:Lipids; C483345:PSAP protein, human; D049231:Saposins; D049128:Sphingolipid Activator Proteins; D001617:beta-Glucosidase