H5N1 strain-specific hemagglutinin CD4+ T cell epitopes restricted by HLA DR4

Vaccine. 2009 Jun 12;27(29):3862-9. doi: 10.1016/j.vaccine.2009.04.019. Epub 2009 May 3.


CD4+ T cells play a pivotal role in the viral immunity, and as such identification of unique strain-specific HLA class II restricted epitopes is essential for monitoring cellular strain-specific viral immunity. Using Tetramer-Guided Epitope Mapping technique, we identified HLA-DR0401 restricted HA epitopes that are strain-specific to H5N1 virion. Two immunodominant epitopes H5HA(441-460) and H5HA(57-76) were identified from in vitro stimulated human PBMC. Both epitopes elicit strong cellular immune responses when HLA-DR0401 transgenic mice are immunized with H5N1 subvirion indicating in vivo naturally processed immunodominant epitopes. The H5HA(57-76) epitope is unique for the H5N1 strain but conserved among all H5N1 clades recommended for vaccine development by World Health Organization. The unique H5HA(57-76) response was uncommon in unexposed individuals and only observed in the naïve T cell subset. Thus, H5N1 strain-specific H5HA(57-76) immunogenic epitope represents a unique marker for monitoring the efficacy of vaccination or as a candidate vaccine peptide.

Publication types

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

MeSH terms

  • Animals
  • CD4-Positive T-Lymphocytes / immunology
  • Cells, Cultured
  • Epitope Mapping
  • Epitopes, T-Lymphocyte / immunology*
  • HLA-DR4 Antigen / immunology*
  • Hemagglutinin Glycoproteins, Influenza Virus / immunology*
  • Humans
  • Influenza A Virus, H5N1 Subtype / immunology*
  • Mice
  • Mice, Transgenic


  • Epitopes, T-Lymphocyte
  • HLA-DR4 Antigen
  • Hemagglutinin Glycoproteins, Influenza Virus
  • hemagglutinin, avian influenza A virus