KIR2DL3 Gene - Structure, Function, and Clinical Significance

KIR2DL3 is a member of the killer cell immunoglobulin-like receptor (KIR) family, expressed on natural killer (NK) cells and a subset of T cells. It functions as an inhibitory receptor by recognizing HLA-C group 1 allotypes (e.g., HLA-Cw*03, HLA-Cw*07, HLA-Cw*08) via its two extracellular immunoglobulin domains. Upon ligand binding, the long cytoplasmic tail containing immunoreceptor tyrosine-based inhibitory motifs (ITIMs) recruits phosphatases such as SHP-1 and SHP-2, suppressing NK cell cytotoxicity and cytokine release. KIR2DL3 plays a critical role in immune surveillance, viral infection control, and regulation of autoimmunity.

Tissue Expression

Cell Line Expression

Hotspot Mutations

Mutation functional classification

• Natural killer cell mediated cytotoxicity (KEGG hsa04650)

• Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell (Reactome R-HSA-198933)

KIR2DL3 is a transmembrane glycoprotein of 348 amino acids (UniProt P43628). It contains two extracellular immunoglobulin-like domains (D1 and D2), a transmembrane region, and a long cytoplasmic tail with two ITIM motifs. The protein is expressed on the surface of NK cells and some T cells. It binds HLA-C molecules bearing the C1 epitope (Asn80). Upon ligand engagement, ITIMs become phosphorylated and recruit SHP-1/SHP-2 phosphatases, inhibiting NK cell effector functions. KIR2DL3 exhibits allelic polymorphism that influences its expression level and ligand-binding affinity, impacting disease susceptibility.