Recombinant Human TLR1 Fc Chimera Protein, CF

The Toll-like family of molecules are type I transmembrane proteins that serve as pattern recognition receptors for microbial pathogens. There are at least eleven mouse and ten human TLRs that activate the innate immune system following exposure to a variety of microbial species (1, 2). TLRs contain a large number of leucine-rich repeats (LRRs) and a cytoplasmic tail with one Toll/IL-1 receptor (TIR) domain. Mature human TLR1 consists of a 556 amino acid (aa) extracellular domain (ECD) with 20 LRRs, a 21 aa transmembrane segment, and a 185 aa cytoplasmic domain (3, 4). Within the ECD, human TLR1 shares 63% aa sequence identity with human TLR6 and 20% -43% aa sequence identitity with human TLR2, -3, -4, -5, -7, -8, -9, and -10. It shares 73% and 71% aa sequence identity with mouse and rat TLR1, respectively. TLR1 is expressed on the surface of macrophages, dendritic cells, and tonsillar epithelial cells in ligand-independent association with TLR2 (5 - 8). TLR2 additionally associates with TLR6 to form a functional complex with specificity for distinct but related microbial ligands (9 - 11). TLR1 and TLR2 cooperate in the recognition of bacterial and protozoal triacylated lipopeptides and glycosylphosphatidylinositols (6, 10 - 12). Ligand binding induces TLR1 localization to lipid rafts followed by receptor internalization and activation of NF kappa B (7, 11, 13).