The CD14 region spanning amino acids 57–64 is critical for interaction with the extracellular Toll-like receptor 2 domain ☆

Abstract CD14 has been shown to enhance Toll-like receptor 2 (TLR2)-mediated signaling in response to peptidoglycan. Anti-CD14 monoclonal antibody MEM-18, whose epitope was located at the amino acid residues 57–64, blocked the binding of sCD14 to the recombinant soluble form of the extracellular TLR2 domain (sTLR2). The deletion mutant sCD14 Δ57–64 lacking the amino acid residues 57–64 failed to bind to sTLR2. Cotransfection of wild type mCD14 but not mCD14 Δ57–64 with TLR2 enhanced NF-κB activation in response to peptidoglycan. These results indicate that the CD14 region spanning amino acids 57–64 is critical for interacting with TLR2 and enhancing TLR2-mediated peptidoglycan signaling.