Inhibitory killer cell immunoglobulin-like receptors (Inhibitory KIRs)

Inhibitory Killer cell Immunoglobulin-like Receptors (KIRs) are a diverse family of transmembrane glycoproteins expressed primarily on Natural Killer (NK) cells and certain subsets of T cells. These receptors play a pivotal role in the immune system by monitoring the expression of Human Leukocyte Antigen (HLA) class I molecules on the surface of host cells. When an inhibitory KIR binds to its cognate HLA ligand, it recruits phosphatases via its cytoplasmic immunoreceptor tyrosine-based inhibitory motifs (ITIMs), which suppress NK cell activation and prevent the lysis of healthy self-cells (Nature Reviews Immunology, 2018). In the context of oncology, many tumor cells maintain HLA expression to exploit this inhibitory pathway and evade immune surveillance. Therapeutic interventions, such as monoclonal antibodies like lirilumab, are designed to block the interaction between inhibitory KIRs and HLA class I molecules. By preventing this inhibitory signaling, these drugs aim to enhance the anti-tumor cytotoxicity of NK cells and promote a more robust immune response against malignancies (Journal of Clinical Oncology, 2017).

Other names

Killer cell inhibitory receptorsCD158KIRKiller cell immunoglobulin-like receptorsKIR2DLKIR3DL

Checkpoint inhibition; blocking the interaction between inhibitory KIRs on NK cells and HLA class I ligands on target cells to restore NK cell-mediated lysis.