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

Andrzej Dzionek, Yoshiaki Sohma, Jun Nagafune, Marina Cella, Marco Colonna, Fabio Facchetti, Gritt Günther, Ian Johnston, Antonio Lanzavecchia, Tomoko Nagasaka, Tsutomu Okada, William Vermi, Gregor Winkels, Terumi Yamamoto, Monika Zysk, Yasunori Yamaguchi, Jürgen Schmitz

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Abstract

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/α 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.

Original languageEnglish
Pages (from-to)1823-1834
Number of pages12
JournalJournal of Experimental Medicine
Volume194
Issue number12
DOIs
StatePublished - Dec 17 2001

Keywords

  • Interferon inducers
  • Interferon type I
  • Magnetic cell sorting
  • Monoclonal antibodies
  • Systemic lupus erythematosus

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