TLR9 antagonist HC4076 is an ODN used to inhibit preferably human Toll-like receptor 9. HC4077 can be used as control reagent. Toll-like receptors (TLRs) are highly conserved from Drosophila to humans and share structural and functional similarities. TLRs constitute of a family of pattern recognition receptors (PRRs) that mediate cellular responses to a large variety of pathogens (viruses, bacteria, and parasites) by specific recognition of so-called ‘pathogen-associated molecular patterns’. Activation of TLRs leads to activation of NFκB-dependent and IFN regulatory factor-dependent signaling pathways. TLRs are differentially expressed among tissues and cell types by various cells of the immune system, such as macrophages and dendritic cells. They recognize and respond to molecules derived from bacterial, viral and fungal pathogens.Whereas most TLRs are expressed on the cell surface, TLR9 is expressed intracellularly within one or more endosomal compartments and recognizes nucleic acids. TLR9 detects a rather subtle difference in the DNA of vertebrates compared with that of pathogens. Vertebrate genomic DNAs have mostly methylated CpG dinucleotides where bacterial and viral DNAs have unmethylated CpG dinucleotides. TLR9 undergoes relocation from endoplasmic reticulum to CpG-ODN-containing endosomes. In these endosomes TLR9 becomes a functional receptor after proteolytic cleavage. TLR9 exists as a preformed homodimer and CpG-ODN binding promotes its conformational change, bringing the cytoplasmic TIR-like domains close to each other. This allows a recruitment of the key adapter protein MyD88 which initiates a signaling cascade.Certain DNA sequences can suppress innate immune activation and have been shown to be effective in eg arthritis and SLE. The TTAGGG repeat is such sequence and is commonly found in mammalian telomeric DNA. Suppressive synthetic ODNs prevent TLR9 activation by binding to unmethylated CpG DNA. ODN A151 functions as a competitive inhibitor by binding to AIM2 and IFI16 and competing with these sensors for stimulatory DNA ligands.