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  • 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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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.).

Author information

Author notes

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

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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The authors declare no competing financial interests.

Corresponding author

Correspondence to Stefan H E Kaufmann.

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https://doi.org/10.1038/ni1035

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