Saposin C is required for lipid presentation by human CD1b

Florian Winau; Vera Schwierzeck; Robert Hurwitz; Natascha Remmel; Peter A. Sieling; Robert L. Modlin; Steven A. Porcelli; Volker Brinkmann; Masahiko Sugita; Konrad Sandhoff; Stefan H.E. Kaufmann; Ulrich E. Schaible

doi:10.1038/ni1035

Saposin C is required for lipid presentation by human CD1b

Florian Winau, Vera Schwierzeck, Robert Hurwitz, Natascha Remmel, Peter A. Sieling, Robert L. Modlin, Steven A. Porcelli, Volker Brinkmann, Masahiko Sugita, Konrad Sandhoff, Stefan H.E. Kaufmann, Ulrich E. Schaible

Microbiology & Immunology

Research output: Contribution to journal › Article › peer-review

150 Scopus citations

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.

Original language	English (US)
Pages (from-to)	169-174
Number of pages	6
Journal	Nature Immunology
Volume	5
Issue number	2
DOIs	https://doi.org/10.1038/ni1035
State	Published - Feb 2004

ASJC Scopus subject areas

Immunology and Allergy
Immunology

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10.1038/ni1035

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@article{62721a77c9cd4325ace8e0a0f1433e26,

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.",

author = "Florian Winau and Vera Schwierzeck and Robert Hurwitz and Natascha Remmel and Sieling, {Peter A.} and Modlin, {Robert L.} and Porcelli, {Steven A.} and Volker Brinkmann and Masahiko Sugita and Konrad Sandhoff and Kaufmann, {Stefan H.E.} and Schaible, {Ulrich E.}",

note = "Funding Information: We thank J.T. Belisle sharing reagents and J. Enders for technical assistance. Supported by the Deutsche Forschungsgemeinschaft (SFB 421, U.E.S. and S.H.E.K.; SPP 1131, U.E.S.). Copyright: Copyright 2008 Elsevier B.V., All rights reserved.",

year = "2004",

month = feb,

doi = "10.1038/ni1035",

language = "English (US)",

volume = "5",

pages = "169--174",

journal = "Nature Immunology",

issn = "1529-2908",

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T1 - Saposin C is required for lipid presentation by human CD1b

AU - Winau, Florian

AU - Schwierzeck, Vera

AU - Hurwitz, Robert

AU - Remmel, Natascha

AU - Sieling, Peter A.

AU - Modlin, Robert L.

AU - Porcelli, Steven A.

AU - Brinkmann, Volker

AU - Sugita, Masahiko

AU - Sandhoff, Konrad

AU - Kaufmann, Stefan H.E.

AU - Schaible, Ulrich E.

N1 - Funding Information: We thank J.T. Belisle sharing reagents and J. Enders for technical assistance. Supported by the Deutsche Forschungsgemeinschaft (SFB 421, U.E.S. and S.H.E.K.; SPP 1131, U.E.S.). Copyright: Copyright 2008 Elsevier B.V., All rights reserved.

PY - 2004/2

Y1 - 2004/2

N2 - 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.

AB - 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.

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Saposin C is required for lipid presentation by human CD1b

Abstract

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