The role of human Dectin-1 in eliciting antigen specific CD8+ T cell responses

Dectin-1 recognizing fungal pathogens and mycobacteria, delivers intracellular signals to activate DCs. Here we report that Dectin-1 expressed on human DCs possesses unique immunological function that potentiates antigen-specific CD8+ T cell responses. We first generated an agonistic anti-Dectin-1 monoclonal antibody (mAb), which recognized Leu192-Asn202 in Dectin-1 and efficiently bound to both in vitro monocyte-derived DCs and in vivo CD1c+ skin dermal DCs, but not Langerin cells. Syk-dependent activation by anti-Dectin-1 mAb induced DCs to upregulate T cell costimulatory molecules, particularly CD70 and 4-1BBL, as well as cytokines and chemokines. This signaling via Dectin-1 allowed DCs to potentiate both memory and naïve CD8+ T cell responses by promoting their expansions and functional activities. Furthermore, both neo- and non-self-antigens delivered to DCs via Dectin-1 resulted in potent antigen-specific CD8+ T cell responses. This was largely dependent on CD70 and 4-1BBL upregulated by the signaling via Dectin-1. We also demonstrated that Dectin-1-mediated activation of DCs did not promote Foxp3+ and IL-10-producing regulatory CD4+ T cell responses, but potentiated CD4+ helper T cell function for inducing effector CD8+ T cells. We conclude that Dectin-1 on human DCs has unique function for eliciting antigen-specific CD8+ T cell responses by taking up antigens and delivering intracellular signals favoring effector CD8+ T cell responses.