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

Vaccine. 2008 Sep 2;26(37):4775-82. doi: 10.1016/j.vaccine.2008.07.012. Epub 2008 Jul 26.

Abstract

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-2K(d)-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 M2(82-90) 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 M2(127-135) 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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Amino Acid Substitution / genetics
  • Amino Acid Substitution / immunology
  • Animals
  • CD8-Positive T-Lymphocytes / immunology*
  • Epitopes, T-Lymphocyte / genetics
  • Epitopes, T-Lymphocyte / immunology*
  • Female
  • Immunodominant Epitopes / genetics
  • Immunodominant Epitopes / immunology*
  • Mice
  • Mice, Inbred BALB C
  • Plasmids
  • Respiratory Syncytial Virus Vaccines / genetics
  • Respiratory Syncytial Virus Vaccines / immunology*
  • Respiratory Syncytial Viruses / immunology*
  • Vaccines, DNA / genetics
  • Vaccines, DNA / immunology
  • Viral Proteins / genetics
  • Viral Proteins / immunology*

Substances

  • Epitopes, T-Lymphocyte
  • Immunodominant Epitopes
  • M2-2 protein, respiratory syncytial virus
  • Respiratory Syncytial Virus Vaccines
  • Vaccines, DNA
  • Viral Proteins