TY - JOUR
T1 - 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
AU - Lahoud, Mireille H.
AU - Proietto, Anna I.
AU - Ahmet, Fatma
AU - Kitsoulis, Susie
AU - Eidsmo, Liv
AU - Wu, Li
AU - Sathe, Priyanka
AU - Pietersz, Suzanne
AU - Chang, Hsuen Wen
AU - Walker, Ian D.
AU - Maraskovsky, Eugene
AU - Braley, Hal
AU - Lew, Andrew M.
AU - Wright, Mark D.
AU - Heath, William R.
AU - Shortman, Ken
AU - Caminschi, Irina
PY - 2009/6/15
Y1 - 2009/6/15
N2 - 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.
AB - 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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U2 - 10.4049/jimmunol.0900464
DO - 10.4049/jimmunol.0900464
M3 - Article
C2 - 19494282
AN - SCOPUS:67649184779
SN - 0022-1767
VL - 182
SP - 7587
EP - 7594
JO - Journal of Immunology
JF - Journal of Immunology
IS - 12
ER -