LILRA2

LILRA2 (leukocyte immunoglobulin-like receptor A2, also ILT1/LIR-7/CD85H) is an activating member of the leukocyte immunoglobulin-like receptor (LILR) family. LILRA2 is a type I transmembrane protein with four extracellular Ig-like domains (two D1-D2 pairs) whose cytoplasmic region lacks ITIMs but whose charged transmembrane arginine associates with the FcεRIγ chain adaptor, delivering activating SYK-mediated signals. LILRA2 is expressed on monocytes, macrophages, neutrophils, basophils and eosinophils. Unlike most LILRs that bind classical HLA class I, LILRA2 recognizes both HLA class I and HLA class II molecules with low affinity, but its most distinctive function is pathogen sensing: it detects Staphylococcus aureus-derived peptides (including the superantigen-like protein SSL7-coated complement C5 complexes and formylated peptides) and neutrophil-derived microvesicles, triggering pro-inflammatory cytokine release, phagocytosis and antimicrobial responses. A soluble splice form of LILRA2 generated by alternative splicing is markedly elevated in synovial fluid of rheumatoid arthritis patients, serving as a biomarker and decoy modulating joint inflammation.