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J. Biol. Chem., Vol. 283, Issue 24, 16693-16701, June 13, 2008

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CLEC9A Is a Novel Activation C-type Lectin-like Receptor Expressed on BDCA3⁺ Dendritic Cells and a Subset of Monocytes^*

From the Division of Immunology, Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Observatory, 7925, South Africa

We describe here the first characterization of CLEC9A, a group V C-type lectin-like receptor located in the "Dectin-1 cluster" of related receptors, which are encoded within the natural killer (NK)-gene complex. Expression of human CLEC9A is highly restricted in peripheral blood, being detected only on BDCA3⁺ dendritic cells and on a small subset of CD14⁺CD16^- monocytes. CLEC9A is expressed at the cell surface as a glycosylated dimer and can mediate endocytosis, but not phagocytosis. CLEC9A possesses a cytoplasmic immunoreceptor tyrosine-based activation-like motif that can recruit Syk kinase, and we demonstrate, using receptor chimeras, that this receptor can induce proinflammatory cytokine production. These data indicate that CLEC9A functions as an activation receptor.

Received for publication, December 5, 2007 , and in revised form, April 10, 2008.

^* This work was supported by the National Research Foundation (South Africa), the Wellcome Trust and scholarships from Harry Crossley, KW Johnston Research, and Marion Beatrice. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

^* Author's Choice—Final version full access.

The on-line version of this article (available at http://www.jbc.org) contains supplemental Figs. S1–S8.

The nucleotide sequence(s) reported in this paper has been submitted to the GenBank^TM/EBI Data Bank with accession number(s) EU339276 [GenBank] , EU339277 [GenBank] , EU339278 [GenBank] , EU339279 [GenBank] , EU339280 [GenBank] , and EU339281.

¹ A Wellcome Trust Senior Research Fellow in Biomedical Science in South Africa. To whom correspondence should be addressed. Tel.: 27-21-4066684; E-mail: gordon.brown{at}mweb.co.za

² The abbreviations used are: CTLD, C-type lectin domain; HA, hemagglutinin; PBS, phosphate-buffered saline; BSA, bovine serum albumin; FITC, fluorescein isothiocyanate; FACS, fluorescent-activated cell sorting; NK, natural killer cells; TNF, tumor necrosis factor; IL, interleukin; DC, dendritic cells; PBMC, peripheral blood mononuclear cells; TRITC, tetramethylrhodamine isothiocyanate; ORF, open reading frame.

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