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

¹ Miltenyi Biotec GmbH, D-51429 Bergisch Gladbach, Germany
² Pharmaceutical Research Laboratory, Kirin Brewery Company, Limited, Gunma 370-1295, Japan
³ Basel Institute for Immunology, CH-4005 Basel, Switzerland
⁴ Department of Pathology, University of Brescia, Spedali Civili Brescia, 1-25124 Brescia, Italy
⁵ Institute for Research in Biomedicine, CH-6500 Bellinzona, Switzerland

Address correspondence to J. Schmitz, Miltenyi Biotec GmbH, Friedrich-Ebert-Strabe 68, D-51429 Bergisch Gladbach, Germany. Phone: 49-2204-8306-410; Fax: 49-2204-85197; E-mail: juergenS{at}miltenyibiotec.de

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 /ß 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 /ß 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 /ß in systemic lupus erythematosus patients.

Key Words: interferon type I • monoclonal antibodies • magnetic cell sorting • interferon inducers • systemic lupus erythematosus

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• Schiffer, L E, Hussain, N, Wang, X, Huang, W, Sinha, J, Ramanujam, M, Davidson, A (2002). Lowering anti-dsDNA antibodies--what's new?. Lupus 11: 885-894 [Abstract]  
• Schjetne, K. W., Thompson, K. M., Aarvak, T., Fleckenstein, B., Sollid, L. M., Bogen, B. (2002). A mouse C{kappa}-specific T cell clone indicates that DC-SIGN is an efficient target for antibody-mediated delivery of T cell epitopes for MHC class II presentation. Int Immunol 14: 1423-1430 [Abstract] [Full Text]  
• Ryan, E. J., Marshall, A. J., Magaletti, D., Floyd, H., Draves, K. E., Olson, N. E., Clark, E. A. (2002). Dendritic Cell-Associated Lectin-1: A Novel Dendritic Cell-Associated, C-Type Lectin-Like Molecule Enhances T Cell Secretion of IL-4. J. Immunol. 169: 5638-5648 [Abstract] [Full Text]  
• Nardelli, B., Zaritskaya, L., Semenuk, M., Cho, Y. H., LaFleur, D. W., Shah, D., Ullrich, S., Girolomoni, G., Albanesi, C., Moore, P. A. (2002). Regulatory Effect of IFN-{kappa}, A Novel Type I IFN, On Cytokine Production by Cells of the Innate Immune System. J. Immunol. 169: 4822-4830 [Abstract] [Full Text]  
• Ebner, S., Hofer, S., Nguyen, V. A., Furhapter, C., Herold, M., Fritsch, P., Heufler, C., Romani, N. (2002). A Novel Role for IL-3: Human Monocytes Cultured in the Presence of IL-3 and IL-4 Differentiate into Dendritic Cells That Produce Less IL-12 and Shift Th Cell Responses Toward a Th2 Cytokine Pattern. J. Immunol. 168: 6199-6207 [Abstract] [Full Text]  
• Geijtenbeek, T. B. H., Engering, A., van Kooyk, Y. (2002). DC-SIGN, a C-type lectin on dendritic cells that unveils many aspects of dendritic cell biology. J. Leukoc. Biol. 71: 921-931 [Abstract] [Full Text]  
• Iyoda, T., Shimoyama, S., Liu, K., Omatsu, Y., Akiyama, Y., Maeda, Y., Takahara, K., Steinman, R. M., Inaba, K. (2002). The CD8+ Dendritic Cell Subset Selectively Endocytoses Dying Cells in Culture and In Vivo. J. Exp. Med. 195: 1289-1302 [Abstract] [Full Text]  

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