The target antigens recognized by the cross-reactive population of cytotoxic T cells on A/USSR/90/77 (H1N1) influenza virus-infected cells was studied with monoclonal antibodies to the H-2k antigen and viral hemagglutinin. The cytotoxic killing of virus-infected cells was differentially inhibited by three monoclonal antibodies to H-2k. Synergistic inhibition of cytotoxic activity was obtained with monoclonal antibodies to H-2 and to some antigenic determinants on the hemagglutinin melecule of A/USSR but not with others. Since target cells infected with other subtypes of influenza A viruses were not inhibited by any of the monoclonal antibodies to A/USSR hemagglutinin, it is suggested that the sites recognized by the cross-reactive cytotoxic T cells were sterically inhibited by the anti-A/USSR monoclonal antibodies. The results suggest that at least one of the target antigens recognized by the cross-reactive population of cytotoxic T cells is located on the hemagglutinin molecule. The present observations are in agreement with cytotoxic T cell recognition of closely situated viral and H-2 determinants.
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