Natural killer cell activating receptor NKp30 (NKp30)

Natural killer cell activating receptor NKp30 (also known as NCR3 or CD337) is a type I transmembrane glycoprotein expressed on all mature NK cells[9]. It is a key member of the natural cytotoxicity receptor (NCR) family, which includes NKp44 and NKp46. NKp30 consists of a single extracellular immunoglobulin (Ig)-like domain, a short stalk region, a transmembrane domain, and a cytoplasmic tail[1][2][3]. The extracellular domain folds into a unique Ig-like β-sandwich (I-type), distinct from the other NCRs, and is a member of the CD28 family, which also includes PD-1 and CTLA-4[1][2]. NKp30 plays a central role in the innate immune surveillance and elimination of tumor and virally infected cells. Its best-characterized ligand is B7-H6, a member of the B7 family, which is expressed on tumor cells but not on healthy cells[1][3]. The interaction between NKp30 and B7-H6 triggers NK cell activation and cytolytic activity. The receptor’s binding interface with B7-H6 involves both the front and back β-sheets of its Ig-like domain, differing from the interactions seen with CD28 family inhibitory receptors[1][3]. NKp30 may also interact with other proposed ligands, including heparan sulfate, viral proteins (e.g., human cytomegalovirus protein pp65), and the parasite protein DBL-1α, but B7-H6 is the most studied and appears most relevant for tumor surveillance[1][7]. NKp30 is implicated in immune responses against cancer and certain infections. Its activity can be modulated by viral and possibly other immune evasion mechanisms, such as disruption of the NKp30–CD3ζ signaling complex by viral proteins[5]. The receptor’s structural and functional characteristics make it an attractive, though not yet clinically exploited, target for cancer immunotherapy[1][3][5]. No direct drugs targeting NKp30 are currently in clinical use, and there are no widely accepted biomarkers for NKp30-targeted therapies.

Other names

NCR3Natural cytotoxicity triggering receptor 3CD337Natural cytotoxicity receptor 3Natural killer protein 30