Natural killer cell activating receptor

Natural killer (NK) cell activating receptors are a diverse group of germline-encoded surface proteins that trigger the cytotoxic activity and cytokine production of NK cells upon binding to their respective ligands. These receptors, which include the natural cytotoxicity receptors (NCRs: NKp46, NKp44, NKp30), NKG2D, and CD16, play a crucial role in the 'missing-self' and 'induced-self' recognition of virally infected or malignantly transformed cells. Unlike T-cell receptors, NK activating receptors do not require MHC-restricted antigen presentation, making them attractive targets for cancer immunotherapy. Therapeutic strategies include bispecific and trispecific NK-cell engagers (BiKEs and TriKEs) that bridge NK cells to tumor antigens, as well as CAR-NK cells engineered to express these receptors. The balance between these activating signals and inhibitory signals (from receptors like KIRs and NKG2A) determines the overall NK cell response, and modulating this balance is a key area of drug development in oncology and infectious diseases.

Other names

Natural cytotoxicity receptorNCRNKG2DNKp46NKp30NKp44CD16DNAM-1Activating NK receptor

Engagement of activating receptors to trigger NK cell-mediated lysis of target cells and secretion of pro-inflammatory cytokines through ITAM-dependent or DAP10-mediated signaling pathways.