TLR9, Human, mAb 5G5, FITC

The monoclonal antibody 5G5 recognizes human Toll-like receptor 9. Toll-like receptors (TLRs) arehighly conserved from Drosophila to humans and share structural and functional similarities. TLRsconstitute of a family of pattern recognition receptors (PRRs) that mediate cellular responses to alarge variety of pathogens (viruses, bacteria, and parasites) by specific recognition of so-called‘pathogen-associated molecular patterns’. Activation of TLRs, a family of at least 11 differentmembersthat function either as homo- or heterodimers, leads to activation of NFκB-dependent and IFNregulatoryfactor-dependent signaling pathways. TLRs have a central role in innate immunity and arealso required for the development of an adaptive immune response. TLRs are expressed by variouscells of the immune system, such as macrophages and dendritic cells. They recognize and respond tomolecules derived from bacterial, viral and fungal pathogens.Whereas most TLRs are expressed on the cell surface, TLR9 is expressed intracellularly within one ormore endosomal compartments and recognizes nucleic acids. TLR9 detects a rather subtle differencein the DNA of vertebrates compared with that of pathogens. Vertebrate genomic DNAs have mostlymethylated CpG dinucleotides where bacterial and viral DNAs have unmethylated CpG dinucleotides.TLR9 undergoes relocation from endoplasmic reticulum to CpG-ODN-containing endosomes. In theseendosomes TLR9 becomes a functional receptor after proteolytic cleavage. TLR9 exists as apreformed homodimer and CpG-ODN binding promotes its conformational change, bringing thecytoplasmic TIR-like domains close to each other. This allows a recruitment of the key adapter proteinMyD88 which initiates a signalling cascade. The only human immune cell types known toconstitutively express TLR9 and to be activated by CpG ODN are pDCs and B cells. TLR9 triggeringinduces an activation phenotype in the B cells and pDCs, characterised by the expression ofcostimulatory molecules, resistance to apoptosis, and induces Th1-type immune response profiles.