Multiple tissue-specific isoforms of sulfatide activate CD1d-restricted type II NKT cells

Authors

  • Maria Blomqvist,

    1. Department of Microbiology and Immunology, Institute of Biomedicine, University of Gothenburg, Gothenburg, Sweden
    Current affiliation:
    1. Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, University of Gothenburg, Sweden
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    • These authors contributed equally to this work

  • Sara Rhost,

    1. Department of Microbiology and Immunology, Institute of Biomedicine, University of Gothenburg, Gothenburg, Sweden
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    • These authors contributed equally to this work

  • Susann Teneberg,

    1. Department of Medical Biochemistry and Cell Biology, Institute of Biomedicine, University of Gothenburg, Gothenburg, Sweden
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  • Linda Löfbom,

    1. Department of Microbiology and Immunology, Institute of Biomedicine, University of Gothenburg, Gothenburg, Sweden
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  • Thomas Østerbye,

    1. Bartholin Institute, Rigshospitalet, Copenhagen, Denmark
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  • Manfred Brigl,

    1. Department of Pathology and Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA
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  • Jan-Eric Månsson,

    1. Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, University of Gothenburg, Sweden
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  • Susanna L. Cardell

    Corresponding author
    1. Department of Microbiology and Immunology, Institute of Biomedicine, University of Gothenburg, Gothenburg, Sweden
    • Department of Microbiology and Immunology, University of Gothenburg, Box 435, 405 30 Gothenburg, Sweden Fax: +46-31-786-6351

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Abstract

The glycosphingolipid sulfatide (SO3-3Galβ1Cer) is a demonstrated ligand for a subset of CD1d-restricted NKT cells, which could regulate experimental autoimmune encephalomyelitis, a murine model for multiple sclerosis, as well as tumor immunity and experimental hepatitis. Native sulfatide is a mixture of sulfatide isoforms, i.e. sulfatide molecules with different long-chain bases and fatty acid chain lengths and saturation. Here, we demonstrate that sulfatide-specific CD1d-restricted murine NKT hybridomas recognized several different sulfatide isoforms. These included the physiologically relevant isoforms C24:1 and C24:0, major constituents of the myelin sheet of the nervous system, and C16:0, prominent in the pancreatic islet β-cells. The most potent sulfatide isoform was lysosulfatide (lacking a fatty acid). Shortened fatty acid chain length (C24:1 versus C18:1), or saturation of the long fatty acid (C24:0), resulted in reduced stimulatory capacity, and fatty acid hydroxylation abolished the response. Moreover, sulfatide was not responsible for the natural autoreactivity toward splenocytes by XV19 T hybridoma cells. Our results reveal a promiscuity in the recognition of sulfatide isoforms by a CD1d-restricted NKT-cell clone, and suggest that sulfatide, a major component of the myelin sheet and pancreatic β-cells, is one of several natural ligands for type II CD1d-restricted NKT cells.

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