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

MH Lahoud, AI Proietto, F Ahmet… - The Journal of …, 2009 - journals.aai.org
MH Lahoud, AI Proietto, F Ahmet, S Kitsoulis, L Eidsmo, L Wu, P Sathe, S Pietersz…
The Journal of Immunology, 2009journals.aai.org
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 …
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.
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