Saposin C is required for lipid presentation by human CD1b.
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.
Winau
Florian
F
Max-Planck-Institute for Infection Biology, Department of Immunology, Schumannstrasse 21-22, D-10117 Berlin, Germany.
Schwierzeck
Vera
V
Hurwitz
Robert
R
Remmel
Natascha
N
Sieling
Peter A
PA
Modlin
Robert L
RL
Porcelli
Steven A
SA
Brinkmann
Volker
V
Sugita
Masahiko
M
Sandhoff
Konrad
K
Kaufmann
Stefan H E
SH
Schaible
Ulrich E
UE
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
D018949:Antigens, CD1; C419394:CD1b antigen; D006023:Glycoproteins; D008055:Lipids; C483345:PSAP protein, human; D049231:Saposins; D049128:Sphingolipid Activator Proteins; D001617:beta-Glucosidase