Blocking of influenza virus-induced cell-mediated cytotoxicity by hemagglutinin-specific monoclonal antibody

The relative importance of three major proteins of influenza virus in the mechanism of induction of cell-mediated cytotoxicity (natural killer cell activity) was assessed by an overnight chromium-51-release assay using radiolabeled K-562 cells as target cells and Ficoll-Hypaque-purified peripheral-blood lymphocytes as effector cells. Incubation of peripheral-blood lymphocytes with influenza virus (whether type-A or type-B) showed that intact and formalin-inactivated influenza virus enhanced cell-mediated cytotoxicity equally. The stimulation by intact or inactivated virions was comparable to that induced by the two major internal mediators of positive natural killer cell regulation, namely interferon and interleukin-2. This virus-induced cell-mediated cytotoxicity, which was mediated by human natural-killer 1+ cells, could be blocked only with monoclonal antibodies to the hemagglutinin and not with antinucleoprotein or antimatrix protein monoclonal antibodies, results indicating that the hemagglutinin of influenza virus is a potent mediator of natural killer cell stimulation in vitro.