Killer cell immunoglobulin-like receptor 2DS1 (KIR2DS1)

Killer cell immunoglobulin-like receptor 2DS1 (KIR2DS1) is a transmembrane glycoprotein expressed primarily on Natural Killer (NK) cells and a subset of T cells. It functions as an activating receptor that specifically recognizes HLA-C2 group ligands, which are characterized by an asparagine residue at position 80 of the alpha-1 helix (UniProt P43631). Upon binding to HLA-C2, KIR2DS1 recruits the signaling adapter DAP12, triggering a cascade that results in NK cell degranulation and the production of pro-inflammatory cytokines such as IFN-gamma (PubMed: 11526147). This receptor plays a critical role in the immune system's ability to detect and destroy virally infected or malignant cells that express HLA-C2. In the context of oncology, KIR2DS1-mediated recognition is particularly significant in allogeneic hematopoietic stem cell transplantation, where KIR-ligand mismatch can enhance the graft-versus-leukemia effect (PubMed: 22343536). Beyond cancer, KIR2DS1 is heavily implicated in reproductive health; its interaction with fetal HLA-C2 on trophoblasts can influence placental vascularization and the risk of preeclampsia (PubMed: 18364370). Current therapeutic research focuses on harnessing KIR2DS1 for CAR-NK cell therapies and modulating its activity to treat both hematologic malignancies and solid tumors.

Other names

CD158hp50.1Killer cell immunoglobulin-like receptor, two domains, short cytoplasmic tail, 1KIR2DS1 receptor

Activation of Natural Killer (NK) cell cytotoxicity and cytokine release (e.g., IFN-gamma) through association with the DAP12 signaling adapter protein upon binding to HLA-C2 group ligands.