Enhancement of the CD8+ T cell response to a subdominant epitope of respiratory syncytial virus by deletion of an immunodominant epitope

Cytotoxic T lymphocytes (CTLs) are critical for the control of respiratory syncytial virus infection (RSV) in humans and mice. Recently, we identified a new H-2Kd-restricted subdominant epitope in the respiratory syncytial virus M2 protein. In this study, we investigated if modification of anchor residues at positions 2 and 9 in the dominant M282-90 epitope in the M2 protein would alter the CTL epitope dominance hierarchy following immunization with plasmid DNA encoding M2 proteins. We showed that immunogenicity of the subdominant epitope M2127-135 was enhanced when the anchor residues of the dominant epitope were mutated, suggesting that the immunodominant epitope induces a suppression of response to the subdominant epitope.