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.
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.
Dzionek
A
A
Miltenyi Biotec GmbH, D-51429 Bergisch Gladbach, Germany.
Sohma
Y
Y
Nagafune
J
J
Cella
M
M
Colonna
M
M
Facchetti
F
F
Günther
G
G
Johnston
I
I
Lanzavecchia
A
A
Nagasaka
T
T
Okada
T
T
Vermi
W
W
Winkels
G
G
Yamamoto
T
T
Zysk
M
M
Yamaguchi
Y
Y
Schmitz
J
J
D000595:Amino Acid Sequence; D000911:Antibodies, Monoclonal / Q000276:immunology; D017951:Antigen Presentation; D003001:Cloning, Molecular; D003713:Dendritic Cells / Q000276:immunology*; D006801:Humans; D016898:Interferon-alpha / Q000276:immunology*; D016899:Interferon-beta / Q000276:immunology*; D037102:Lectins / Q000235:genetics / Q000276:immunology; D037181:Lectins, C-Type; D008180:Lupus Erythematosus, Systemic / Q000276:immunology; D008562:Membrane Glycoproteins; D008969:Molecular Sequence Data; D011971:Receptors, Immunologic; D011975:Receptors, Mitogen / Q000276:immunology
D000911:Antibodies, Monoclonal; C443299:CLEC4C protein, human; D016898:Interferon-alpha; D037102:Lectins; D037181:Lectins, C-Type; D008562:Membrane Glycoproteins; D011971:Receptors, Immunologic; D011975:Receptors, Mitogen; D016899:Interferon-beta