Description
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)