The C-type lectin Clec12A present on mouse and human dendritic cells can serve as a target for antigen delivery and enhancement of antibody responses

Mireille H. Lahoud, Anna I. Proietto, Fatma Ahmet, Susie Kitsoulis, Liv Eidsmo, Li Wu, Priyanka Sathe, Suzanne Pietersz, Hsuen Wen Chang, Ian D. Walker, Eugene Maraskovsky, Hal Braley, Andrew M. Lew, Mark D. Wright, William R. Heath, Ken Shortman, Irina Caminschi

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79 Citations (Scopus)

Abstract

We have cloned the mouse and human C-type lectin Clec12A, expressed both, and produced mAb recognizing both. Mouse Clec12A is highly expressed on splenic CD8+ dendritic cells (DC) and plasmacytoid DC. A proportion of CD8-DC also expresses lower levels of Clec12A, as do monocytes, macrophages, and B cells. Human CLEC12A, like the mouse counterpart, is expressed on blood monocytes and DC, including pDC and BDCA-3+DC, the proposed equivalent of mouse CD8+DC. To determine whether Ag targeted to Clec12A could induce immune responses, mice were injected with a rat mAb recognizing Clec12A, or a control rat mAb, then production of anti-rat Ig was measured. Anti-Clec12A mAb alone produced only moderate responses, but these were amplified by coinjecting only small amounts of LPS as a DC activation agent. Furthermore, when OVA was conjugated to anti-Clec12A mAb, OVA-specific T cells were induced to proliferate. This Ag presentation to naive T cells was due to targeting conventional DC, because their ablation eliminated T cell activation. The potent Ab responses induced using microgram amounts of anti-Clec12A and minimal amounts of adjuvant demonstrate that this molecule can be used as an Ag-delivery target to enhance Ab responses to vaccines.

Original languageEnglish
Pages (from-to)7587-7594
Number of pages8
JournalJournal of Immunology
Volume182
Issue number12
DOIs
Publication statusPublished - Jun 15 2009
Externally publishedYes

ASJC Scopus subject areas

  • Immunology

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    Lahoud, M. H., Proietto, A. I., Ahmet, F., Kitsoulis, S., Eidsmo, L., Wu, L., Sathe, P., Pietersz, S., Chang, H. W., Walker, I. D., Maraskovsky, E., Braley, H., Lew, A. M., Wright, M. D., Heath, W. R., Shortman, K., & Caminschi, I. (2009). The C-type lectin Clec12A present on mouse and human dendritic cells can serve as a target for antigen delivery and enhancement of antibody responses. Journal of Immunology, 182(12), 7587-7594. https://doi.org/10.4049/jimmunol.0900464