Human plasmacytoid dendritic cells (PDC) are believed to link innate and adaptive immunity by producing type I interferon (IFN‐I) and triggering adaptive T cell‐mediated immunity. However, it remains elusive to which degree both PDC functions are linked. Here we show that CMV antigen targeted to PDC using a CD303 (blood dendritic cell antigen 2, BDCA‐2) mAb is rapidly endocytosed and traffics via early sorting endosomes to emerging MHC‐enriched compartments. Both processes occur independently of TLR ligand stimulation. Restimulation of CMV‐specific CD4⁺ effector‐memory T helper cells by autologous PDC and induction of IFN‐I production in PDC are dependent on appropriate stimulation. Type B CpG oligonucleotide (CpG‐B)‐stimulated PDC efficiently process and present CMV antigen and are thus capable of stimulating CMV‐specific effector‐memory T helper cells. CpG‐A‐stimulated PDC produce large amounts of IFN‐I and express programmed death receptor‐1 ligand 1. CpG‐A plus CpG‐B‐co‐stimulated PDC behave like CpG‐B‐stimulated PDC, suggesting that antigen processing and presentation in PDC is dependent on stimulation that concurrently inhibits IFN‐I production. In vivo targeting of antigens to PDC via CD303 combined with appropriate PDC stimulation may allow induction of specific T cell activation.

Supporting Information for this article is available at http://www.wiley‐vch.de/contents/jc_2040/2008/37552_s.pdf