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 Chi Yi Lo, Alexandra Rizzitelli, Li Wu, David Vremec, Serani LH van Dommelen, Ian K Campbell, Eugene Maraskovsky, Hal Braley, Gayle M Davey, Patricia L Mottram, Nicholas C van de Velde, Kent Jensen, Andrew M Lew, Mark Dexter Wright, William R HeathKen Shortman, Mireille H Lahoud

Research output: Contribution to journalArticleResearchpeer-review

282 Citations (Scopus)

Abstract

A novel dendritic cell (DC)-restricted molecule, Clec9A, was identified by gene expression profiling of mouse DC subtypes. Based on sequence similarity, a human ortholog was identified. Clec9A encodes a type II membrane protein with a single extracellular C-type lectin domain. Both the mouse Clec9A and human CLEC9A were cloned and expressed, and monoclonal antibodies (mAbs) against each were 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.
Original languageEnglish
Pages (from-to)3264 - 3273
Number of pages10
JournalBlood
Volume112
Issue number8
DOIs
Publication statusPublished - 2008

Cite this

Caminschi, I., Proietto, A. I., Ahmet, F., Kitsoulis, S., Teh, J. S., Lo, J. C. Y., Rizzitelli, A., Wu, L., Vremec, D., van Dommelen, S. LH., Campbell, I. K., Maraskovsky, E., Braley, H., Davey, G. M., Mottram, P. L., van de Velde, N. C., Jensen, K., Lew, A. M., Wright, M. D., ... Lahoud, M. H. (2008). The dendritic cell subtype-restricted C-type lectin Clec9A is a target for vaccine enhancement. Blood, 112(8), 3264 - 3273. https://doi.org/10.1182/blood-2008-05-155176.