Activating receptor on natural killer cell

Activating receptors on natural killer (NK) cells comprise a heterogeneous group of cell surface proteins that signal the immune system to identify and destroy virally infected or malignant cells. Major families include the natural cytotoxicity receptors (NCRs: NKp46, NKp44, NKp30); C-type lectin-like receptors (such as NKG2D and CD94-NKG2C); killer immunoglobulin-like receptors (KIRs, e.g., KIR2DS1); and the low-affinity Fc receptor CD16 (FcγRIIIa)[1][2][3][4][5][6][7]. These receptors recognize stress-induced ligands upregulated by cells under transformation or infection, leading to release of cytolytic granules and pro-inflammatory cytokines. Activating receptors frequently require co-stimulation or signaling through adaptor molecules such as DAP12 or CD3ζ, which trigger downstream activation via ITAM motifs[2][3][6]. NK cell activity is tightly regulated by a balance of activating and inhibitory signals; dysregulation can result in autoimmunity or loss of cancer surveillance. While targeting individual activating receptors is being explored for cancer immunotherapy—such as anti-CD16 therapy to boost ADCC—there is currently no single "activating receptor on natural killer cell" as a canonical molecule, but rather a group of receptors with similar biological outcomes.

Other names

Killer activation receptorNatural cytotoxicity receptorNKp30NKp44NKp46NKG2DCD16DNAM-1CD226CD94-NKG2CKIR2DS12B4 (CD244)CRACC (SLAMF7)NTB-A (SLAMF6)CD27CD100CD160

Induction of antibody-dependent cellular cytotoxicity (ADCC), activation of cytolytic granule release, cytokine production, recognition and lysis of abnormal (infected or tumor) cells