Concomitant Activation and Antigen Uptake via Human Dectin-1 Results in Potent Antigen-Specific CD8+ T Cell Responses
Open Access
- 15 September 2010
- journal article
- Published by The American Association of Immunologists in The Journal of Immunology
- Vol. 185 (6), 3504-3513
- https://doi.org/10.4049/jimmunol.1000999
Abstract
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.Keywords
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