The C-type lectin receptor CLEC9A mediates antigen uptake and (cross-)presentation by human blood BDCA3+ myeloid dendritic cells

Gerty Schreibelt, Lieke J J Klinkenberg, Luis J Cruz, Paul J Tacken, J. Tel, Martin Kreutz, Gosse J Adema, Gordon D Brown, Carl G Figdor, I Jolanda M de Vries

Onderzoeksoutput: Bijdrage aan tijdschriftTijdschriftartikelAcademicpeer review

199 Citaten (Scopus)
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Samenvatting

CLEC9A is a recently discovered C-type lectin receptor involved in sensing necrotic cells. In humans, this receptor is selectively expressed by BDCA3(+) myeloid dendritic cells (mDCs), which have been proposed to be the main human cross-presenting mDCs and may represent the human homologue of murine CD8(+) DCs. In mice, it was demonstrated that antigens delivered with antibodies to CLEC9A are presented by CD8(+) DCs to both CD4(+) and CD8(+) T cells and induce antitumor immunity in a melanoma model. Here we assessed the ability of CLEC9A to mediate antigen presentation by human BDCA3(+) mDCs, which represent < 0.05% of peripheral blood leukocytes. We demonstrate that CLEC9A is only expressed on immature BDCA3(+) mDCs and that cell surface expression is lost after TLR-mediated maturation. CLEC9A triggering via antibody binding rapidly induces receptor internalization but does not affect TLR-induced cytokine production or expression of costimulatory molecules. More importantly, antigens delivered via CLEC9A antibodies to BDCA3(+) mDCs are presented by both MHC class I (cross-presentation) and MHC class II to antigen-specific T cells. We conclude that CLEC9A is a promising target for in vivo antigen delivery in humans to increase the efficiency of vaccines against infectious or malignant diseases.

Originele taal-2Engels
Pagina's (van-tot)2284-92
Aantal pagina's9
TijdschriftBlood : the Journal of Hematology
Volume119
Nummer van het tijdschrift10
DOI's
StatusGepubliceerd - 8 mrt. 2012

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