Targeting antigen to bone marrow stromal cell-2 expressed by conventional and plasmacytoid dendritic cells elicits efficient antigen presentation

Authors

  • Jessica M. Moffat,

    1. Walter and Eliza Hall Institute, Parkville, Victoria, Australia
    2. Department of Microbiology and Immunology, The University of Melbourne, Parkville, Victoria, Australia
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  • Elodie Segura,

    1. Institut National de la Sante et de la Recherche Medicale Unite 932, Paris, France
    2. Center de Recherche, Institut Curie, Paris, France
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  • Gabriela Khoury,

    1. Department of Medicine, Monash University, Victoria, Australia
    2. Centre for Virology, Burnet Institute, Prahran, Victoria, Australia
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  • Irene Caminschi,

    1. Walter and Eliza Hall Institute, Parkville, Victoria, Australia
    2. Center for Immunology, Burnet Institute, Prahran, Victoria, Australia
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  • Paul U. Cameron,

    1. Centre for Virology, Burnet Institute, Prahran, Victoria, Australia
    2. Department of Infectious Diseases, Monash University, Victoria, Australia
    3. Infectious Diseases Unit, Alfred Hospital, Prahran, Victoria, Australia
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  • Sharon R. Lewin,

    1. Centre for Virology, Burnet Institute, Prahran, Victoria, Australia
    2. Department of Infectious Diseases, Monash University, Victoria, Australia
    3. Infectious Diseases Unit, Alfred Hospital, Prahran, Victoria, Australia
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  • Jose A. Villadangos,

    Corresponding author
    1. Department of Microbiology and Immunology, The University of Melbourne, Parkville, Victoria, Australia
    2. Department of Biochemistry and Molecular Biology, The University of Melbourne, Parkville, Victoria, Australia
    • Walter and Eliza Hall Institute, Parkville, Victoria, Australia
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  • Justine D. Mintern

    Corresponding author
    1. Department of Biochemistry and Molecular Biology, The University of Melbourne, Parkville, Victoria, Australia
    • Walter and Eliza Hall Institute, Parkville, Victoria, Australia
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Full correspondence: Dr. Justine D. Mintern, The University of Melbourne, Bio21, 30 Flemington Rd, Parkville Victoria 3010, Australia

Fax: +61-3-9348-1421

e-mail: jmintern@unimelb.edu.au

Additional correspondence: Prof. Jose A. Villadangos, The University of Melbourne, Bio21, 30 Flemington Rd, Parkville Victoria 3010, Australia

Fax: +61-3-9348-1421

e-mail: j.villadangos@unimelb.edu.au

Abstract

Bone marrow stromal cell-2 (BST-2) has major roles in viral tethering and modulation of interferon production. Here we investigate BST-2 as a receptor for the delivery of antigen to dendritic cells (DCs). We show that BST-2 is expressed by a panel of mouse and human DC subsets, particularly under inflammatory conditions. The outcome of delivering antigen to BST-2 expressed by steady state and activated plasmacytoid DC (pDC) or conventional CD8+ and CD8 DCs was determined. T-cell responses were measured for both MHC class I (MHCI) and MHC class II (MHCII) antigen presentation pathways in vitro. Delivering antigen via BST-2 was compared with that via receptors DEC205 or Siglec-H. We show that despite a higher antigen load and faster receptor internalisation, when antigen is delivered to steady state or activated pDC via BST-2, BST-2-targeted activated conventional DCs present antigen more efficiently. Relative to DEC205, BST-2 was inferior in its capacity to deliver antigen to the MHCI cross-presentation pathway. In contrast, BST-2 was superior to Siglec-H at initiating either MHCI or MHCII antigen presentation. In summary, BST-2 is a useful receptor to target with antigen, given its broad expression pattern and ability to access both MHCI and MHCII presentation pathways with relative efficiency.

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