Natural killer cell activating receptor ligand

NK activating receptor ligands is an umbrella term for a diverse group of stress-inducible cell surface proteins expressed by infected, transformed, or stressed cells and recognized by activating receptors on natural killer (NK) cells. These ligands are not a single molecular entity but include several unrelated protein families such as MICA, MICB, ULBPs (ligands for NKG2D), PVR and Nectin-2 (ligands for DNAM-1), and other still uncharacterized molecules. Engagement of these ligands by their cognate receptors (NKG2D, DNAM-1, NKp30, NKp44, NKp46, and others) triggers NK cell activation, leading to cytotoxicity, cytokine secretion, and immunosurveillance. Expression of these ligands is typically low on healthy cells but is upregulated by cellular stress, infection, or malignant transformation, facilitating immune targeting. However, tumors and pathogens can evade immune recognition by downregulating ligand expression or shedding soluble forms, which represents a major therapeutic challenge.

Other names

NK cell activating ligandActivating NK ligandNKG2D ligandNCR ligandDNAM-1 ligandULBPMICA/BPVR (CD155, ligand for DNAM-1)Nectin-2 (CD112, ligand for DNAM-1)AICL (ligand for NKp80)

Enhancement of NK cell recognition and killing of tumor or infected cells (by upregulating or mimicking ligand presentation); Inhibition of NK cell receptors or blockade of ligand shedding to prevent tumor immune escape