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PMID: 11748283 Published · ppublish English Journal Article

BDCA-2, a novel plasmacytoid dendritic cell-specific type II C-type lectin, mediates antigen capture and is a potent inhibitor of interferon alpha/beta induction.

The Journal of experimental medicine ·Vol. 194 ·No. 12 ·2001-12-17 ·Pages 1823-34

Dzionek A, Sohma Y, Nagafune J, Cella M, Colonna M, Facchetti F, Günther G, Johnston I, Lanzavecchia A, Nagasaka T, Okada T, Vermi W, Winkels G, Yamamoto T, Zysk M, Yamaguchi Y, Schmitz J

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 alpha/beta 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 alpha/beta 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 alpha/beta in systemic lupus erythematosus patients.

MeSH Terms
Amino Acid Sequence Antibodies, Monoclonal/immunology Antigen Presentation Cloning, Molecular Dendritic Cells/immunology Humans Interferon-alpha/immunology Interferon-beta/immunology Lectins/genetics,immunology Lectins, C-Type Lupus Erythematosus, Systemic/immunology Membrane Glycoproteins Molecular Sequence Data Receptors, Immunologic Receptors, Mitogen/immunology
Chemicals
Antibodies, Monoclonal CLEC4C protein, human Interferon-alpha Lectins Lectins, C-Type Membrane Glycoproteins Receptors, Immunologic Receptors, Mitogen Interferon-beta
Authors & Affiliations
17 authors, click to expand affiliations / ORCID
Dzionek A
Miltenyi Biotec GmbH, D-51429 Bergisch Gladbach, Germany.
Sohma Y
Nagafune J
Cella M
Colonna M
Facchetti F
Günther G
Johnston I
Lanzavecchia A
Nagasaka T
Okada T
Vermi W
Winkels G
Yamamoto T
Zysk M
Yamaguchi Y
Schmitz J
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Article Info
Journal
The Journal of experimental medicine
Abbr.
J Exp Med
ISSN
0022-1007
DOI
10.1084/jem.194.12.1823
Published
2001-12-17
Pages
1823-34
Language
English
Region
United States
NLM ID
2985109R
PMCID
PMC2193584
Subset
IM
Corrections
CommentIn
PMID: 11748288
External Links
PubMed source DOI: 10.1084/jem.194.12.1823 PMC Full Text View journal details
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