antigen uptake, dectin-1,responces

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Published online August 20, 2010

The Journal of Immunology, 2010, 185, 3504 -3513

by The American Association of Immunologists, Inc.

doi:10.4049/jimmunol.1000999

Concomitant Activation and Antigen Uptake via Human Dectin-1 Results in Potent

Antigen-Specific CD8+ T Cell Responses

Ling Ni,* Ingrid Gayet,* Zurawski,* Dorothee Duluc,* Anne-Laure Flamar,*

Xiao-Hua Li,* Amy O'Bar,* Clayton,* Karolina Palucka,*,,, Gerard

Zurawski,*, Jacques Banchereau,*,,, and SangKon Oh*,

*Baylor Institute for Immunology Research; INSERM Unité 899, Dallas, TX 75204;

and Clinical Immunology Division, Department of Medicine and Department of Gene

and Cell Medicine, Immunology Institute, Mount Sinai School of Medicine, New

York, NY 10029

Dectin-1, a C-type lectin recognizing fungal and mycobacterial pathogens, can

deliver intracellular signals that activate dendritic cells (DCs), resulting in

initiation of immune responses and expansion of Th17 CD4+ T cell responses. In

this paper, we studied the roles of human Dectin-1 (hDectin-1) expressed on DCs

in the induction and activation of Ag-specific CD8+ T cell responses. We first

generated an agonistic anti–hDectin-1 mAb, which recognizes the hDectin-1

Glu143-Ile162 region. It bound to in vitro monocyte-derived DCs and to in vivo

CD1c+CD1a+ dermal DCs but not to epidermal Langerhans cells.

Anti–hDectin-1–mediated DC activation resulted in upregulation of costimulatory

molecules and secretion of multiple cytokines and chemokines in a Syk-dependent

manner. DCs activated with the anti–hDectin-1 mAb could significantly enhance

both neo and foreign Ag-specific CD8+ T cell responses by promoting both the

expansion of CD8+ T cells and their functional activities. We further

demonstrated that delivering Ags to DCs via hDectin-1 using anti–hDectin-1-Ag

conjugates resulted in potent Ag-specific CD8+ T cell responses. Thus, hDectin-1

expressed on DCs can contribute to the induction and activation of cellular

immunity against intracellular pathogens, such as mycobacteria, that are

recognized by DCs via Dectin-1. Vaccines based on delivering Ags to DCs with an

agonistic anti–hDectin-1 mAb could elicit CD8+ T cell-mediated immunity.

Address correspondence and reprint requests to Dr. SangKon Oh, Baylor Institute

for Immunology Research, 3434 Live Oak, Dallas, TX 75204. E-mail address:

sangkono@...

This work was supported by National Institutes of Health Grants U19 AI057234 and

R01 CA078846 and the Baylor Health Care System Foundation. J.B. holds the W.W.

Caruth, Jr., Chair for Transplantation Immunology Research.

The online version of this article contains supplemental material.

Abbreviations used in this paper:

AP, alkaline phosphatase; Coh, cohesion; DC, dendritic cell; Doc, dockerin; Flu,

influenza viral; h, human; LC, Langerhans cell; mDC, myeloid dendritic cell;

Syk, spleen tyrosine kinase.

http://www.jimmunol.org/cgi/content/abstract/185/6/3504