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

A Dzionek, Y Sohma, J Nagafune, M Cella… - The Journal of …, 2001 - rupress.org
A Dzionek, Y Sohma, J Nagafune, M Cella, M Colonna, F Facchetti, G Günther, I Johnston…
The Journal of experimental medicine, 2001rupress.org
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 …
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.
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