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.
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.
Lahoud
Mireille H
MH
The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia.
Proietto
Anna I
AI
Ahmet
Fatma
F
Kitsoulis
Susie
S
Eidsmo
Liv
L
Wu
Li
L
Sathe
Priyanka
P
Pietersz
Suzanne
S
Chang
Hsuen-Wen
HW
Walker
Ian D
ID
Maraskovsky
Eugene
E
Braley
Hal
H
Lew
Andrew M
AM
Wright
Mark D
MD
Heath
William R
WR
Shortman
Ken
K
Caminschi
Irina
I
D000818:Animals; D000917:Antibody Formation / Q000276:immunology*; D017951:Antigen Presentation / Q000276:immunology; D000941:Antigens / Q000276:immunology*; D002462:Cell Membrane / Q000276:immunology; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology*; D006801:Humans; D037181:Lectins, C-Type / Q000276:immunology*; D007962:Leukocytes / Q000276:immunology; D051379:Mice; D011975:Receptors, Mitogen / Q000276:immunology*
D000941:Antigens; C485220:CLEC12A protein, human; C529398:CLEC12A protein, mouse; D037181:Lectins, C-Type; D011975:Receptors, Mitogen