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Saposin C is required for lipid presentation by human CD1b

Nature Immunology volume 5, pages 169–174 (2004)Cite this article

A Corrigendum to this article was published on 01 March 2004

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.

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Figure 1: Generation of APCs from human fibroblasts.
Figure 2: Antigen-specific activation of lipid-reactive T cell clones.
Figure 3: The effect of SAP-C in antigen presentation is not dependent on β-glucosidase activity.
Figure 4: Subcellular localization of LAM, SAP-C and CD1b.
Figure 5: SAP-C extracts LAM from membranes.
Figure 6: Molecular interactions between SAP-C and CD1b.

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Acknowledgements

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.).

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Author notes

  1. Florian Winau and Vera Schwierzeck: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Immunology, Max-Planck-Institute for Infection Biology, Schumannstraβe 21-22, Berlin, D-10117, Germany

    Florian Winau, Vera Schwierzeck, Stefan H E Kaufmann & Ulrich E Schaible

  2. Max-Planck-Institute for Infection Biology, Central Core Facility Protein Biochemistry, Schumannstraβe 21-22, Berlin, D-10117, Germany

    Robert Hurwitz

  3. Kekulé Institute of Organic Chemistry and Biochemistry, Gerhard-Domagk-Straβe 1, Bonn, D-53121, Germany

    Natascha Remmel & Konrad Sandhoff

  4. Division of Dermatology, Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, 90095, California, USA

    Peter A Sieling & Robert L Modlin

  5. Department of Microbiology and Immunology, Albert Einstein College of Medicine, New York, 10461, New York, USA

    Steven A Porcelli

  6. Max-Planck-Institute for Infection Biology, Central Core Facility Microscopy, Schumannstraβe 21-22, Berlin, D-10117, Germany

    Volker Brinkmann

  7. Department of Microbiology and Immunology, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-ku, 113-8602, Tokyo, Japan

    Masahiko Sugita

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  1. Florian Winau
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Correspondence to Stefan H E Kaufmann.

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Winau, F., Schwierzeck, V., Hurwitz, R. et al. Saposin C is required for lipid presentation by human CD1b. Nat Immunol 5, 169–174 (2004). https://doi.org/10.1038/ni1035

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