BDCA-2, a Novel Plasmacytoid Dendritic Cell–specific Type II C-type Lectin, Mediates Antigen Capture and Is a Potent Inhibitor of Interferon α/β Induction

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  • Andrzej Dzionek
    1Miltenyi Biotec GmbH, D-51429 Bergisch Gladbach, Germany
  • Yoshiaki Sohma
    2Pharmaceutical Research Laboratory, Kirin Brewery Company, Limited, Gunma 370-1295, Japan
  • Jun Nagafune
    2Pharmaceutical Research Laboratory, Kirin Brewery Company, Limited, Gunma 370-1295, Japan
  • Marina Cella
    3Basel Institute for Immunology, CH-4005 Basel, Switzerland
  • Marco Colonna
    3Basel Institute for Immunology, CH-4005 Basel, Switzerland
  • Fabio Facchetti
    4Department of Pathology, University of Brescia, Spedali Civili Brescia, 1-25124 Brescia, Italy
  • Gritt Günther
    1Miltenyi Biotec GmbH, D-51429 Bergisch Gladbach, Germany
  • Ian Johnston
    1Miltenyi Biotec GmbH, D-51429 Bergisch Gladbach, Germany
  • Antonio Lanzavecchia
    5Institute for Research in Biomedicine, CH-6500 Bellinzona, Switzerland
  • Tomoko Nagasaka
    2Pharmaceutical Research Laboratory, Kirin Brewery Company, Limited, Gunma 370-1295, Japan
  • Tsutomu Okada
    2Pharmaceutical Research Laboratory, Kirin Brewery Company, Limited, Gunma 370-1295, Japan
  • William Vermi
    4Department of Pathology, University of Brescia, Spedali Civili Brescia, 1-25124 Brescia, Italy
  • Gregor Winkels
    1Miltenyi Biotec GmbH, D-51429 Bergisch Gladbach, Germany
  • Terumi Yamamoto
    2Pharmaceutical Research Laboratory, Kirin Brewery Company, Limited, Gunma 370-1295, Japan
  • Monika Zysk
    1Miltenyi Biotec GmbH, D-51429 Bergisch Gladbach, Germany
  • Yasunori Yamaguchi
    2Pharmaceutical Research Laboratory, Kirin Brewery Company, Limited, Gunma 370-1295, Japan
  • Jürgen Schmitz
    1Miltenyi Biotec GmbH, D-51429 Bergisch Gladbach, Germany

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<jats:p>Plasmacytoid dendritic cells are present in lymphoid and nonlymphoid tissue and contribute substantially to both innate and adaptive immunity. Recently, we have described several monoclonal antibodies that recognize a plasmacytoid dendritic cell-specific antigen, which we have termed BDCA-2. Molecular cloning of BDCA-2 revealed that BDCA-2 is a novel type II C-type lectin, which shows 50.7% sequence identity at the amino acid level to its putative murine ortholog, the murine dendritic cell–associated C-type lectin 2. Anti–BDCA-2 monoclonal antibodies are rapidly internalized and efficiently presented to T cells, indicating that BDCA-2 could play a role in ligand internalization and presentation. Furthermore, ligation of BDCA-2 potently suppresses induction of interferon α/β production in plasmacytoid dendritic cells, presumably by a mechanism dependent on calcium mobilization and protein-tyrosine phosphorylation by src-family protein-tyrosine kinases. Inasmuch as production of interferon α/β by plasmacytoid dendritic cells is considered to be a major pathophysiological factor in systemic lupus erythematosus, triggering of BDCA-2 should be evaluated as therapeutic strategy for blocking production of interferon α/β in systemic lupus erythematosus patients.</jats:p>

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