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Blood, 15 October 2008, Vol. 112, No. 8, pp. 3264-3273.
Prepublished online as a Blood First Edition Paper on July 30, 2008; DOI 10.1182/blood-2008-05-155176.
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Submitted May 2, 2008
Accepted July 19, 2008
The dendritic cell subtype restricted C-type lectin Clec9A is a target for vaccine enhancement
Irina Caminschi*, Anna I Proietto, Fatma Ahmet, Susie Kitsoulis, Joo Shin Teh, Jennifer C.Y. Lo, Alexandra Rizzitelli, Li Wu, David Vremec, Serani L.H. van Dommelen, Ian K Campbell, Eugene Maraskovsky, Hal Braley, Gayle M Davey, Patricia Mottram, Nicholas van de Velde, Kent Jensen, Andrew M. Lew, Mark D. Wright, William R Heath, Ken Shortman, and Mireille H Lahoud
Immunology Division, Walter and Eliza Hall Institute, Melbourne, Victoria, Australia
Dept Biochemistry & Molecular Biology, Monash University, Melbourne, Victoria, Australia
CSL Limited, Bio21 Institute, Melbourne, Victoria, Australia
Austin Hospital, Burnet Institute, Melbourne, Victoria, Australia
Human Immunology Laboratory, Schering-Plough Biopharma, Palo Alto, California, United States
Department of Immunology, Monash University, Melbourne, Victoria, Australia
* Corresponding author; email: caminschi{at}wehi.edu.au.
A novel dendritic cell (DC)-restricted molecule, Clec9A, was identified by gene expression profiling of mouse DC subtypes. Based on sequence similarity, a human orthologue was identified. Clec9A encodes a type II membrane protein with a single extracellular C-type lectin domain. Both the mouse and human Clec9A were cloned and expressed, and monoclonal antibodies (mAbs) against each generated. Surface staining revealed that Clec9A was selective for mouse DCs and was restricted to the CD8+ conventional DC and plasmacytoid DC subtypes. A subset of human blood DCs also expressed CLEC9A. A single injection of mice with a mAb against Clec9A, which targets antigens (Ags) to the DCs, produced a striking enhancement of antibody responses in the absence of added adjuvants or danger signals, even in mice lacking Toll-like receptor signaling pathways. Such targeting also enhanced CD4 and CD8 T-cell responses. Thus Clec9A serves as a new marker to distinguish subtypes of both mouse and human DCs. Furthermore, targeting Ags to DCs with antibodies to Clec9A is a promising strategy to enhance the efficiency of vaccines, even in the absence of adjuvants.
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