Killer cell immunoglobulin-like receptor (KIR) (KIR)

Killer cell immunoglobulin-like receptors (KIRs) are a multigene family of cell surface glycoproteins found primarily on natural killer (NK) cells and some T cell subsets (UniProt). They function as key regulators of NK cell activity by binding to MHC class I molecules (HLA-A, -B, and -C) on target cells (PubMed: 11847342). Inhibitory KIRs recognize self-MHC molecules and prevent NK cell-mediated lysis of healthy cells, while activating KIRs can trigger cytotoxicity against infected or transformed cells (StatPearls). In haploidentical hematopoietic stem cell transplantation, the absence of recipient HLA ligands for donor inhibitory KIRs (KIR-HLA mismatch) allows donor NK cells to attack residual leukemic cells, providing a potent graft-versus-leukemia effect (PubMed: 11847342). Pharmacological targeting of KIRs, primarily through monoclonal antibodies like lirilumab, seeks to block inhibitory signaling to unleash NK cell activity against various cancers (ClinicalTrials.gov: NCT01687712).

Other names

CD158Killer cell inhibitory receptorKIR familyKiller cell immunoglobulin-like receptor family

Checkpoint inhibition by blocking inhibitory KIR-HLA interactions to enhance natural killer cell-mediated cytotoxicity against tumor cells.