KIR2DL1

KIR2DL1 (Killer Cell Immunoglobulin-Like Receptor 2DL1), also designated CD158a, is an inhibitory receptor predominantly expressed on natural killer (NK) cells and subsets of T lymphocytes. It recognizes specific HLA-C allotypes carrying the C2 epitope (e.g., HLA-Cw*04, -Cw*06) through its immunoglobulin-like extracellular domains. Upon ligand engagement, KIR2DL1 transmits inhibitory signals via immunoreceptor tyrosine-based inhibition motifs (ITIMs) in its cytoplasmic tail, recruiting SHP-1/SHP-2 phosphatases to suppress NK cell cytotoxicity and cytokine production. This interaction maintains self-tolerance but may facilitate immune evasion in malignancies and viral infections. Polymorphisms in KIR2DL1 and its HLA ligands influence outcomes in hematopoietic stem cell transplantation, autoimmune disorders (e.g., rheumatoid arthritis), and infectious diseases (e.g., HIV progression). Therapeutic strategies targeting KIR2DL1 include antagonistic antibodies (e.g., lirilumab) to block inhibitory signaling, currently under evaluation in Phase II trials for hematologic malignancies. Emerging evidence also links KIR2DL1 allelic variants to checkpoint inhibitor responsiveness in solid tumors.