NKp46

NKp46, also known as NCR1, is an activating receptor expressed primarily on natural killer (NK) cells and, to a lesser extent, on some other innate lymphocytes. It is a member of the natural cytotoxicity receptor (NCR) family, which also includes NKp30 and NKp44. The human NCR1 gene encodes the NKp46 protein, a type I transmembrane glycoprotein with extracellular immunoglobulin-like domains that signals through the ITAM-containing adaptor molecule DAP12.

NKp46 is widely used as a phenotypic marker for NK cells in humans and mice. It is expressed at high levels on resting NK cells and can be upregulated upon activation. The receptor transmits activating signals via DAP12, leading to NK cell degranulation and production of cytokines such as interferon-gamma, contributing to cytotoxic responses against target cells.

Ligand recognition by NKp46 is context-dependent and not fully mapped. A well-established ligand is the hemagglutinin protein of influenza A virus, which enables NK cells to recognize and respond to infected cells. Additional ligands on virus-infected or transformed cells are less clearly defined, and research continues to define the full spectrum of NKp46 interactors, including potential glycosylated or stress-induced ligands.

Clinical and research relevance: NKp46 plays a key role in antiviral immunity and tumor immunosurveillance through NK cell activation. Alterations in NKp46 expression or function have been observed in certain infections and cancers. The receptor is used as a standard NK cell marker in immunophenotyping and is being explored as a potential target in immunotherapeutic strategies.