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

By A. Dzionek, Y. Sohma, J. Nagafune, M. Cella, M. Colonna, F. Facchetti, G. Günther, I. Johnston, A. Lanzavecchia, T. Nagasaka and 7 more. Journal of Experimental Medicine, 2001

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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.

Subfields: Immunology

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In Immunology

Citations in the corpus

Signalling through C-type lectin receptors: shaping immune responses (2009, background): “For example, patients with systemic lupus erythematosus (sLe) have significantly reduced numbers of BDCA2-expessing pDCs, and this might account for the excessive production of type I IFNs by pDCs, which is a major pathophysiological factor in sLe, as BDCA2 signalling inhibits TLR-induced type I IFN”
Immunomodulatory functions of type I interferons (2012, background): “In addition, antibodies specific for blood DC antigen 2 (BDCA2; also known as CLEC4C) suppressed the production of type I IFNs by pDCs through the activation of SRC family protein tyrosine kinases, and this also inhibited the activation of autoreactive T cells and the development of skin lesion”
Plasmacytoid dendritic cells: sensing nucleic acids in viral infection and autoimmune diseases (2008, background): “BDCA2 (blood DC antigen 2) is a C-type lectin that is uniquely expressed on the surface of human pDCs and was the first receptor shown to potently suppress the ability of pDCs to produce type I IFNs in response to TLR ligand”
Dendritic-cell-based therapeutic cancer vaccines. (2013, background): “Three cell-surface markers characterize blood DCs: CD303, expressed on plasmacytoid DCs (pDCs), and CD1c and CD141, both expressed on circulating DCs (Dzionek et al., 2000; Dzionek et al., 2001; MacDonald et al., 2002).”
Dendritic cells as therapeutic vaccines against cancer (2005, background): “; interstitial DCs express DC-SIGN (dendritic-cell-specific intercellular-adhesion-molecule-3-grabbing non-integrin), which is involved in interactions with T cells and in DC migration but is also used by pathogens (such as HIV) to hijack the immune system; and pDCs express yet another lectin, BDCA2”
Plasmacytoid predendritic cells initiate psoriasis through interferon-α production (2005, background): “For this purpose, we took advantage of the anti–BDCA-2 monoclonal antibody that specifically binds to human PDCs and suppresses their ability to secrete IFN- (29).”
Efficient Targeting of Protein Antigen to the Dendritic Cell Receptor DEC-205 in the Steady State Leads to Antigen Presentation on Major Histocompatibility Complex Class I Products and Peripheral CD8+ T Cell Tolerance (2002, background): “Other receptors are more DC restricted, e.g., Langerin or CD207 (25), DC-SIGN or CD209 (26, 27), an asialoglycoprotein receptor (28), and BDCA-2 (29), but at this time, these receptors have not been shown to mediate the selective presentation of antigens on the MHC class I and II products of DCs in ”