| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
* The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, Victoria, Australia;
Centre for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden;
IP Australia, Phillip Australian Capital Territory, Australia;
National Health Research Institutes, Miaoli County, Taiwan;
¶ 45 Heller Street, West Brunswick, Australia;
|| CSL, Melbourne, Australia;
# Department of Immunology, Monash University, Melbourne, Australia; and
** Department of Microbiology and Immunology, University of Melbourne, Melbourne, Australia
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.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This study was supported by grants from the National Health and Medical Research Council of Australia.
2 Address correspondence and reprint requests to Dr. Irina Caminschi and Mireille H. Lahoud, The Walter and Eliza Hall Institute of Medical Research, 1G, Royal Parade, Parkville, Victoria 3050, Australia. E-mail addresses: caminschi{at}wehi.edu.au and lahoud{at}wehi.edu.au
3 Abbreviations used in this paper: DC, dendritic cell; cDC, conventional DC; CHO, Chinese hamster ovary; CI, confidence interval; DT, diphtheria toxin; DTR, DT receptor; int, intermediate; MadCam, mucosal addressin cell adhesion molecule; pDC, plasmacytoid DC; PI, propidium iodide; SA, streptavidin; SIGN, specific ICAM-3 grabbing nonintegrin.
4 The online version of this article contains supplemental material.
This article has been cited by other articles:
|
|
 |
|
  S. A. Kaden, S. Kurig, K. Vasters, K. Hofmann, K. S. Zaenker, J. Schmitz, and G. Winkels Enhanced Dendritic Cell-Induced Immune Responses Mediated by the Novel C-Type Lectin Receptor mDCAR1 J. Immunol., October 15, 2009; 183(8): 5069 - 5078. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
