Killer cell immunoglobulin-like receptor 2DL (KIR2DL)

Killer cell immunoglobulin-like receptor 2DL (KIR2DL) family members are inhibitory receptors expressed on the surface of natural killer (NK) cells. These receptors contain two immunoglobulin-like domains and a long cytoplasmic tail with immunoreceptor tyrosine-based inhibition motifs (ITIMs), which, upon engagement with specific HLA class I ligands (e.g., HLA-C allotypes), transmit inhibitory signals to prevent NK cell-mediated lysis of healthy self-cells[1][4][5]. KIR2DL receptors are critical for self-tolerance, the immune response to virally infected or transformed cells, and play important roles in the context of hematopoietic stem cell transplantation, autoimmune disease, and cancer immunotherapy. Notably, KIR2DL4 is an unusual subtype with both inhibitory and activation-related features, primarily involved in cytokine secretion rather than cytotoxic activity[3][4]. Antibodies targeting inhibitory KIRs (such as lirilumab) are being studied to enhance NK cell anti-tumor activity by preventing KIR-mediated suppression[4].

Other names

Killer cell immunoglobulin-like receptor 2DL1/2DL2/2DL3/2DL4KIR2DLCD158a/b/c/dNatural killer cell inhibitory receptor

Inhibitory KIRs (including KIR2DL subtypes) transmit signals via immunoreceptor tyrosine-based inhibition motifs (ITIMs) after binding HLA class I ligands, suppressing NK cell cytotoxicity\nSome anti-KIR antibodies block KIR-HLA interactions to enhance NK cell activity against tumors