Natural cytotoxicity receptor (refers collectively to a family: NKp30, NKp44, and NKp46 receptors) (NCR (individual members: NKp30, NKp44, NKp46; also referred by CD markers: CD337 for NKp30, CD336 for NKp44, CD335 for NKp46))

Natural cytotoxicity receptors (NCRs) comprise a family of germline-encoded, immunoglobulin-like, type I transmembrane receptors most prominently expressed on natural killer (NK) cells, including NKp30 (NCR3), NKp44 (NCR2), and NKp46 (NCR1). NCRs are key activating receptors that recognize a wide range of ligands induced upon cellular stress, transformation, or infection, and transduce potent signals resulting in the cytotoxic elimination of target cells and the secretion of inflammatory cytokines. Initially thought to be restricted to NK cells, they are also expressed on certain subsets of T cells and innate lymphoid cells, with expression and function modulated by cytokines and microenvironmental factors. The major isoforms have both activating and, via alternative splice variants, inhibitory functions; regulation of their balance is implicated in cancer outcomes, infectious diseases, autoimmunity, and pregnancy. NCRs are under intensive study as both immunotherapeutic targets and biomarkers, especially in the context of engineered NK cell therapeutics and tumor immunosurveillance.

Other names

NCRsNKp30 (NCR3, CD337)NKp44 (NCR2, CD336)NKp46 (NCR1, CD335)

Activation (or inhibition) of NK cell cytotoxicity and cytokine secretion upon receptor engagement with stress- or pathology-induced ligands on target cells; antibody-dependent cellular cytotoxicity (ADCC, via association with Fc receptors such as CD16); potential roles in modulation of other immune effectors