Roles of influenza virus infectivity and glycosylation of viral antigen for recognition of target cells by cytolytic T lymphocytes.
The influenza virus strains A/JAP (H2N2) and the recombinant strain A/JAP/BEL (H2N1) were tested before and after UV-light inactivation for their ability to sensitize target cells for cytotoxic T-cell lysis (CTL). Infectious preparations were efficient sensitizers for both specific and cross-reactive CTL, exposure of the cells to even low doses of virus resulting in almost maximum susceptibility. When inactivated, however, A/JAP/BEL was about 10 times more efficient than A/JAP at sensitizing the cells for specific CTL; neither sensitized the cells for cross-reactive CTL. Thus factors other than or in addition to a cleaved haemagglutinin (HA) molecule are important in the fusion of the virus with the cell membrane. Target cells which were infected with virus and exposed to different concentrations of tunicamycin, which inhibits glycosylation, became susceptible to CTL by both specific and cross-reactive effector cells through to a lesser extent than controls. Infected cells showed both strong haemadsorption and cocapping of the HA with K, D gene products. Both of these properties were greatly diminished in the presence of even low concentrations of tunicamycin. Analysis of binding studies using labelled monoclonal anti-HA IgG showed that, in the presence of tunicamycin, the total amount of HA expressed at the cell surface was not reduced, but there was an increase in the dissociation constant of the reaction between expressed HA and antibody. This latter finding was thought to reflect a conformational change in the HA antigen, which might be the reason for the reduced susceptibility to CTL.
D000818:Animals; D000956:Antigens, Viral / Q000276:immunology*; D001666:Binding Sites, Antibody; D050260:Carbohydrate Metabolism; D003602:Cytotoxicity, Immunologic; D005260:Female; D006183:H-2 Antigens / Q000276:immunology; D006388:Hemagglutinins / Q000276:immunology; D007111:Immunity, Cellular; D007152:Immunologic Capping / Q000187:drug effects; D009980:Influenza A virus / Q000276:immunology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009976:Orthomyxoviridae Infections / Q000276:immunology*; D012756:Sheep; D013601:T-Lymphocytes / Q000276:immunology; D014415:Tunicamycin / Q000494:pharmacology
D000956:Antigens, Viral; D006183:H-2 Antigens; D006388:Hemagglutinins; D014415:Tunicamycin