Addition of a prominent epitope affects influenza A virus-specific CD8 T cell immunodominance hierarchies when antigen is limiting

Abstract

A reverse genetics strategy was used to insert the OVA peptide (amino acid sequence SIINFEKL; OVA257-264) into the neuraminidase stalk of both the A/PR8 (H1N1) and A/HK×31 (H3N2) influenza A viruses. Initial characterization determined that KbOVA257 is presented on targets infected with PR8-OVA and HK-OVA without significantly altering D b nucleoprotein (NP)366 presentation. There were similar levels of KbOVA257- and DbNP 366-specific CTL expansion following both primary and secondary intranasal challenge. Interestingly, while variable, the presence of the immunodominant KbOVA257-specific response resulted in diminished Db acidic polymerase224- and Kb basic polymerase subunit I703-, but not ..