Concomitant activation and antigen uptake via human Dectin-1 results in potent antigen-specific CD8+ T cell responses

Ling Ni, Ingrid Gayet, Sandra Zurawski, Dorothee Duluc, Anne Laure Flamar, Xiao Hua Li, Amy O'Bar, Sandra Clayton, Anna Karolina Palucka, Gerard Zurawski, Jacques Banchereau, Sang Kon Oh

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50 Scopus citations

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. Copyright

Original languageEnglish (US)
Pages (from-to)3504-3513
Number of pages10
JournalJournal of Immunology
Volume185
Issue number6
DOIs
StatePublished - Sep 15 2010

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Ni, L., Gayet, I., Zurawski, S., Duluc, D., Flamar, A. L., Li, X. H., O'Bar, A., Clayton, S., Palucka, A. K., Zurawski, G., Banchereau, J., & Oh, S. K. (2010). Concomitant activation and antigen uptake via human Dectin-1 results in potent antigen-specific CD8+ T cell responses. Journal of Immunology, 185(6), 3504-3513. https://doi.org/10.4049/jimmunol.1000999