NKp30

NKp30, also known as natural cytotoxicity triggering receptor 3 (NCR3), is an activating receptor expressed on natural killer (NK) cells and some other lymphocytes. It belongs to the natural cytotoxicity receptor (NCR) family and contributes to the innate immune response by recognizing stressed, infected, or transformed cells and promoting NK cell–mediated cytotoxicity and cytokine production. The NCR family receptors act as part of the early warning system that helps NK cells distinguish abnormal cells from healthy ones.

The most well-characterized ligand for NKp30 is B7-H6, a tumor-associated protein that binds NKp30 and triggers NK cell activation. Other ligands have been proposed, including molecules on virus-infected or transformed cells; however, the extent and physiological relevance of these interactions remain under investigation and not all proposed ligands have been consistently validated.

Signaling through NKp30 occurs after ligand engagement and involves association with ITAM-containing adaptor proteins, such as CD3ζ and FcεRIγ, which transduce activating signals. This leads to downstream pathways that drive degranulation and the release of cytotoxic molecules (e.g., perforin, granzymes) as well as cytokine production, notably interferon-γ (IFN-γ) and tumor necrosis factor (TNF).

NKp30 expression can be modulated during NK cell activation and in various clinical contexts. It exists in multiple splice variants, which can differentially affect receptor function and NK cell responses. In cancer and chronic infections, altered NKp30 expression or isoform patterns have been associated with changes in anti-tumor and antiviral immunity, making NKp30 a focus of interest for immunotherapy and prognostic studies.