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¹ Laboratory of Molecular Immunology, Clinical Research Institute of Montréal, Montréal, Quebec H2W 1R7, Canada
² Department of Microbiology and Immunology, McGill University, Montréal, Quebec H3G IY6, Canada
³ Department of Gastroenterology, Research Institute, International Medical Center of Japan, Shinjuku-ku, Tokyo 162-8655, Japan
⁴ Department of Human Genetics and McGill Centre for the Study of Host Resistance, McGill University, Montréal, Quebec H3A 2B4, Canada
⁵ Cancer and Inflammation Program, Laboratory of Experimental Immunology, Center for Cancer Research, National Cancer Institute at Frederick, Frederick, MD 21702

CORRESPONDENCE Andrew P. Makrigiannis: makriga{at}ircm.qc.ca

Plasmacytoid dendritic cells (pDCs) are an important source of type I interferon (IFN) during initial immune responses to viral infections. In mice, pDCs are uniquely characterized by high-level expression of Ly49Q, a C-type lectin-like receptor specific for class I major histocompatibility complex (MHC) molecules. Despite having a cytoplasmic immunoreceptor tyrosine-based inhibitory motif, Ly49Q was found to enhance pDC function in vitro, as pDC cytokine production in response to the Toll-like receptor (TLR) 9 agonist CpG-oligonucleotide (ODN) could be blocked using soluble monoclonal antibody (mAb) to Ly49Q or H-2K^b. Conversely, CpG-ODN–dependent IFN- production by pDCs was greatly augmented upon receptor cross-linking using immobilized anti-Ly49Q mAb or recombinant H-2K^b ligand. Accordingly, Ly49Q-deficient pDCs displayed a severely reduced capacity to produce cytokines in response to TLR7 and TLR9 stimulation both in vitro and in vivo. Finally, TLR9-dependent antiviral responses were compromised in Ly49Q-null mice infected with mouse cytomegalovirus. Thus, class I MHC recognition by Ly49Q on pDCs is necessary for optimal activation of innate immune responses in vivo.

L.-H. Tai and M.-L. Goulet contributed equally to this paper.

© 2008 Tai et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.jem.org/misc/terms.shtml). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).

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