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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


Lahoud, MH; Proietto, AI; Ahmet, F; Kitsoulis, S; Eidsmo, L; Wu, L; Sathe, P; Pietersz, S; Chang, HW; Walker, ID; Maraskovsky, E; Braley, H; Lew, AM; Wright, MD; Heath, WR; Shortman, K; Caminschi, I
2009-06-15
JOURNAL OF IMMUNOLOGY
Journal Article
182
12
7587-7594
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 d etermine 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 LIPS 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. The Journal of Immunology, 2009, 182: 7587-7594.
AMER ASSOC IMMUNOLOGISTS
IN-VIVO DEPLETION; T-CELLS; CROSS-PRESENTATION; IMMUNE-RESPONSES; MICL CLEC12A; RECEPTOR; CD8(+); INDUCTION; CD4; IDENTIFICATION
10.4049/jimmunol.0900464
Refer to copyright notice on published article.

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Creation Date 2009-06-15 12:00:00