Augmentation of human natural killer cell activity by influenza virus antigens produced in Escherichia coli

A series of Escherichia coli cloned influenza viral gene products were assayed for their ability to augment human natural cytotoxicity in overnight cultures (18 h) at 37 degrees C. Nylon wool nonadherent peripheral blood mononuclear cells (PBMC) proved responsive to stimulation by a number of cloned viral proteins, the most effective being the nonstructural (NS1) protein (but not NS2 protein) and haemagglutinin and matrix antigen components fused to the N-terminal 81 amino acid sequence of NS1. Furthermore, interferon (IFN) was generated in cultures in which enhanced cytotoxicity was detected and was identified as mostly IFN alpha (greater than 90%) with less than 10% IFN gamma contamination. The cell type responding to antigen stimulation was present in Percoll fractions enriched for large granular lymphocytes (LGLs); furthermore PBMC activated by NS1 protein fractionated in the low density Percoll fractions (LGL enriched). Using specific anti-IFN antisera, it was shown that IFN alpha but not IFN gamma was responsible for the enhancement of cytotoxicity. Interferon induction and activation of cytotoxicity could not be ascribed to the presence of contaminating bacterial products. These results suggest that a particular NS1 protein configuration is capable of activating human natural killer cells via the induction of IFN alpha.