Cytotoxic T cells to type A influenza virus; viral hemagglutinin induces A‐strain specificity while infected cells confer cross‐reactive cytotoxicity

This paper deals with the generation and specificity of cytotoxic T cells directed to cells infected with type A influenza viruses. Mice were primed in vivo and their spleen cells restimulated in vitro. Four type A viruses with serologically distinct surface proteins are equally effective in secondary stimulation of cytotoxicity regardless of the viral strain used for priming. The resulting cytotoxic cells will lyse cells infected with any of the 4 type A viruses. Cross‐reactivity between type A and B influenza viruses does not occur. Competition experiments show that the cross‐reactive cytotoxic T cells contain a minor population of cells with increased affinity for the type A virus strain used for priming, but the majority of the cells do not distinguish between the type A virus strains. Virus replication is not required for the secondary generation of cytotoxic T cells; inactivated virus and viral hemagglutinin can serve as stimulators. Hemagglutinin derived from type A/Jap/Bel selects cytotoxic cells with specificity restricted to A/Jap/Bel originally used for priming and A/Jap which shares the hemagglutinin. This secondary stimulation can be achieved only when either of those two type A viruses are used for priming. The results indicate that hemagglutinin is one of the viral proteins recognized by cytotoxic T cells; however, it is not clear which viral protein(s) are responsible for cross‐reactivity.