The C-type lectin receptor CLEC9A mediates antigen uptake and (cross-)presentation by human blood BDCA3+ myeloid dendritic cells.
Publication year
2012Source
Blood, 119, 10, (2012), pp. 2284-92ISSN
Publication type
Article / Letter to editor

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Organization
Tumorimmunology
Paediatrics - OUD tm 2017
Medical Oncology
Journal title
Blood
Volume
vol. 119
Issue
iss. 10
Page start
p. 2284
Page end
p. 92
Subject
NCMLS 2: Immune Regulation; ONCOL 3: Translational research NCMLS 2: Immune RegulationAbstract
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.
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- Academic publications [229037]
- Electronic publications [111437]
- Faculty of Medical Sciences [87745]
- Open Access publications [80287]
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