A five-amino-acid motif in the undefined region of the TLR8 ectodomain is required for species-specific ligand recognition

Toll-like receptors play important roles in regulating immunity against microbial Infections Toll-like receptor 8 (TLR8) belongs to a subfamily comprising TLR7, TLR8 and TLR9 Human TLR8 mediates anti-viral immunity by recognizing ssRNA vu uses. and triggers potent anti-viral and antitumor immune responses upon ligation by synthetic small molecular weight ligands Interestingly, distinct from human TLR8. mouse TLR8 was nor responsive to ligand stimulation in the absence of polyT-oligodeoxynucleotides (polyT-ODN) The molecular basis for this distinct ligand recognition is still unclear In the present Study, we compared the activation of TLR8 from different species including mouse, rat, human, bovine. porcine, horse, sheep, and cat by ligand ligations. Only the TLR8s from the rodent species (i e, Mouse and rat TLR8s) failed to respond to ligand stimulation in the absence of polyT-ODN Multiple sequence alignment analysis suggested that these two rodent TLR8s lack a five-amino-acid motif that is conserved in the non-rodent species with varied sequence This small motif is located in an undefined region of the hTLR8 ectodomain, immediately following LRR-14 Deletion mutation analysis Suggested that this motifs essential for the species-specific ligand recognition of hTLR8, whereas it is not required for self-dimerization and intracellular localization of this receptor (C) 2009 Elsevier Ltd All rights reserved