Plasmacytoid Dendritic Cells Prime Naive Cd4+And Cd8+T Cells After Antigen Uptake Via Mpdca-1

Plasmacytoid Dendritic cells (PDC) produce large amounts of IFN upon microbial stimulation and are believed to link innate and adaptive immune responses. However, it remains controversial whether PDC are in fact able to prime naïve T cells. Here we investigated the function of the recently described PDC‐specific receptor mPDCA‐1. Ligation of mPDCA‐1 with specific mAb resulted in a rapid internalization of the complex. Targeting of PDC with OVA‐conjugated anti‐mPDCA‐1 mAb, but not with an equivalent amount of soluble OVA or OVA conjugated to isotype control antibody, resulted in strong proliferation of OVA‐specific naïve CD4+ T cells. The same was also observed for OVA‐specific naïve CD8+ T cells. Blocking the receptor with excess of unconjugated anti‐mPDCA‐1 mAb inhibited priming of CD4+ and CD8+ T cells. These results indicate that mPDCA‐1 may serve as an antigen uptake receptor delivering its ligands for MHC‐I and MHC‐II presentation. Interestingly, processing and presentation of antigens taken up via mPDCA‐1 was strongly dependent on stimulation, since only activated but not immature PDC were able to prime naïve antigen‐specific T cells. In contrast, antigen uptake was independent on activation as unstimulated PDC also internalized the mAb‐receptor complex. Our results demonstrate that PDC take up and process antigen for efficient priming of CD4+ and CD8+ T cells and thus combine innate and adaptive function.