Identification of a unique TLR2-interacting peptide motif in a microbial leucine-rich repeat protein

► Leucine-rich repeat (LRR) domain of a bacterial protein activates TLR2. ► Peptide repeats in the LRR domain responsible for TLR2 activation were identified. ► A common peptide motif in these repeats interacts with TLR2. ► This peptide motif in a TLR2-dependent manner activates macrophages. ► This study identifies a novel non-acylated peptide ligand of TLR2.