Killer cell immunoglobulin-like receptor 2DS2 (KIR2DS2)

Killer cell immunoglobulin-like receptor 2DS2 (KIR2DS2) is an activating transmembrane glycoprotein expressed mainly on natural killer (NK) cells, classified as part of the immunoglobulin superfamily and functioning as a key recognition element of the innate immune system. Unlike its closely related inhibitory counterparts, KIR2DS2 activates NK cell cytotoxic responses upon recognizing specific human leukocyte antigen (HLA) class I ligands, particularly HLA-C group 1 (C1) alleles and HLA-A*11:01, in a peptide-dependent manner. KIR2DS2 signals through association with the DAP12 adapter, which contains immunoreceptor tyrosine-based activation motifs (ITAMs), to trigger NK cell effector functions like cytokine release and target cell lysis. Genetic polymorphisms in KIR2DS2 and its HLA ligands are linked to susceptibility or protection in several diseases, including cancer, viral infections (e.g., hepatitis C), autoimmune conditions, and pregnancy-related disorders. Although not currently targeted by approved drugs, KIR2DS2 is of growing therapeutic interest due to its role in modulating NK responses in immunotherapy and transplantation settings.

Other names

Killer immunoglobulin-like receptor 2DS2KIR-2DS2Activating KIR2DS2CD158j (less commonly)

Modulation of NK cell cytotoxicity through ligand (HLA class I, especially HLA-C1 group and HLA-A*11:01) recognition leading to activating signaling via DAP12 ITAM-containing adaptor