TLR9 recognizes DNAs with unmethylated CpG motifs and activates innate immune responses.
Ohto et al. identify another TLR9 binding motif, the 5′-xCx DNA motif, and determine
the tertiary structure of TLR9 in complex with CpG and 5′-xCx DNAs to reveal a cooperative
activation mechanism of TLR9 by two types of DNAs.