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, Jurjen Tel, Martin Kreutz, Gosse J Adema, Gordon D Brown, Carl G Figdor, I Jolanda M de Vries

Research output: Contribution to journalArticle

140 Citations (Scopus)

Abstract

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 anti-tumor immunity in a melanoma model. Here we assessed the ability of CLEC9A to mediate antigen presentation by human BDCA3+ mDCs, which represent less than 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 Toll-like receptor-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.
Original languageEnglish
Pages (from-to)2284-2292
Number of pages9
JournalBlood
Volume119
Issue number10
Early online date10 Jan 2012
DOIs
Publication statusPublished - Mar 2012

    Fingerprint

Cite this

Schreibelt, G., Klinkenberg, L. J. J., Cruz, L. J., Tacken, P. J., Tel, J., Kreutz, M., ... de Vries, I. J. M. (2012). The C type lectin receptor CLEC9A mediates antigen uptake and (cross-)presentation by human blood BDCA3+ myeloid dendritic cells. Blood, 119(10), 2284-2292. https://doi.org/10.1182/blood-2011-08-373944