TLR7 and TLR8 are members of the Toll-like-receptor (TLR) family recognizing pathogen-associated molecular patterns.
1,7 The natural ligands of TLR7 and TLR8, double- or single-stranded RNA, can be mimicked by short synthetic oligoribonucleotides (ORNs).
2-5 RNA motifs activating either TLR7 or TLR8 only or both, TLR7 and TLR8, have been described.
In human cells, TLR7 is predominantly expressed in pDCs and B cells, whereas TLR8 is mainly expressed on cells of the myeloid lineage, such as monocytes, macrophages, and myeloid dendritic cells (mDCs). In mice, TLR7 is also expressed on mDCs and monocytes. Murine TLR8 is functionally impaired.
1,7 Due to the sensitive nature of RNA, most nucleic acid TLR7/8 agonists need to be formulated with cationic lipids in order to activate an appropiate immune response. The recommended cationic lipid is DOTAP-Cl (1,2-Dioleoyloxy-3-trimethylammonium-propane chloride).
ORN R-2176-dT as well as ORN R-2176-dT Control can be used without prior complexation to DOTAP.
TLR7 and TLR8 agonists can be used for the activation of immune cells, such as human PBMCs, murine splenocytes, or isolated immune cells, e.g., B cells, pDCs, mDCs, and monocytes.
Control ORNs with similar sequences and identical backbone but no induction of sequence-specific signaling allow for control of unspecific sequence or backbone effects.
