Differential processing and presentation of the H-2D(b)-restricted epitopefrom two different strains of influenza virus nucleoprotein

The influenza virus strains A/NT/60/68 and A/PR/8/34 both have an immunodom inant D-b-restricted epitope in their nucleoprotein (NP) at amino acid resi dues 366-374, with two amino acid differences between the epitopes, Cross-r eactive cytotoxic T lymphocytes (CTLs) were generated by priming mice with the influenza virus A/NT/60/68 NP and restimulating in vitro with influenza virus A/PR/8/34, CTLs that gave high levels of specific lysis recognized t arget cells infected with either strain of influenza virus with similar eff iciency. Surprisingly, when target cells were infected with recombinant vac cinia viruses (VV) expressing the two different NPs, presentation of the D- b-restricted epitope from the A/NT/60/68 NP was extremely poor, whereas pre sentation of the equivalent epitope from the A/PR/8/34 NP was as efficient as in influenza virus-infected cells. This difference was observed in spite of the fact that the two NP sequences show 94% identity at the amino acid sequence level. Experiments with additional cross-reactive CTL cell lines w hich recognized target cells less efficiently revealed a similar difference in presentation between the two NP epitopes in influenza virus-infected ce lls and showed a difference in the efficiency of presentation of the D-b-re stricted epitope from the two NP molecules independent of VV infection. The results show that two equivalent epitopes in highly similar proteins are p rocessed with very different efficiency, even though they are both immunodo minant epitopes, They also suggest that the previously described inhibition of antigen presentation by VV is a general, non-specific effect, which is more apparent for epitopes that are processed and presented less efficientl y.