Inhibitory killer cell immunoglobulin-like receptor 2D (KIR2D)

Inhibitory killer cell immunoglobulin-like receptor 2D (KIR2D) is a family of cell surface receptors primarily expressed on natural killer (NK) cells and some T cell subsets. These receptors contain two extracellular immunoglobulin-like domains and a long cytoplasmic tail with immunoreceptor tyrosine-based inhibitory motifs (ITIMs), enabling them to transmit inhibitory signals upon engagement with their ligands, which are specific epitopes on HLA-C class I molecules[3][5][7]. By recognizing self-HLA class I molecules, KIR2D receptors suppress the cytotoxic activity of NK cells, preventing attacks on healthy autologous cells and acting as key immune checkpoints in the regulation of anti-tumor and anti-viral immunity. Therapeutic blockade of inhibitory KIR2D, notably using the monoclonal antibody lirilumab (IPH2101), has been explored as an immune checkpoint strategy to enhance NK cell responses in cancer. However, trials have shown limited efficacy and raise concerns about possible disruption of immune self-tolerance[1][2][5][7]. KIR2D receptor-ligand interactions, as well as KIR2D expression on NK cells, serve as important biomarkers for patient stratification in immunotherapy approaches.

Other names

KIR2Dinhibitory KIR2D receptorKIR2DL (includes KIR2DL1, KIR2DL2, KIR2DL3, KIR2DL4)killer-cell immunoglobulin-like receptor 2DiKIR2D

Monoclonal antibodies block KIR2D interaction with HLA class I ligands, unleashing NK cell-mediated cytotoxicity against tumor or infected cells Checkpoint inhibition to enhance immune cell activity