CTL epitopes for influenza A including the H5N1 bird flu; genome-, pathogen-, and HLA-wide screening

Vaccine. 2007 Apr 12;25(15):2823-31. doi: 10.1016/j.vaccine.2006.12.038. Epub 2006 Dec 29.

Abstract

The purpose of the present study is to perform a global screening for new immunogenic HLA class I (HLA-I) restricted cytotoxic T cell (CTL) epitopes of potential utility as candidates of influenza A-virus diagnostics and vaccines. We used predictions of antigen processing and presentation, the latter encompassing 12 different HLA class I supertypes with >99% population coverage, and searched for conserved epitopes from available influenza A viral protein sequences. Peptides corresponding to 167 predicted peptide-HLA-I interactions were synthesized, tested for peptide-HLA-I interactions in a biochemical assay and for influenza-specific, HLA-I-restricted CTL responses in an IFN-gamma ELISPOT assay. Eighty-nine peptides could be confirmed as HLA-I binders, and 13 could be confirmed as CTL targets. The 13 epitopes, are highly conserved among human influenza A pathogens, and all of these epitopes are present in the emerging bird flu isolates. Our study demonstrates that present technology enables a fast global screening for T cell immune epitopes of potential diagnostics and vaccine interest. This technology includes immuno-bioinformatics predictors with the capacity to perform fast genome-, pathogen-, and HLA-wide searches for immune targets. To exploit this new potential, a coordinated international effort to analyze the precious source of information represented by rare patients, such as the current victims of bird flu, would be essential.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Aged
  • Animals
  • Birds
  • Epitopes, T-Lymphocyte / immunology*
  • Female
  • Genetic Testing
  • Genome, Viral
  • HLA-A Antigens / immunology*
  • HLA-B Antigens / immunology*
  • Humans
  • Influenza A Virus, H5N1 Subtype / genetics
  • Influenza A Virus, H5N1 Subtype / immunology*
  • Influenza A virus / genetics
  • Influenza A virus / immunology*
  • Influenza in Birds / virology
  • Influenza, Human / blood
  • Influenza, Human / immunology*
  • Influenza, Human / virology
  • Male
  • Membrane Transport Proteins / immunology
  • Membrane Transport Proteins / metabolism
  • Middle Aged
  • Proteasome Endopeptidase Complex / metabolism
  • T-Lymphocytes, Cytotoxic / immunology*
  • T-Lymphocytes, Cytotoxic / virology

Substances

  • Epitopes, T-Lymphocyte
  • HLA-A Antigens
  • HLA-B Antigens
  • Membrane Transport Proteins
  • tapasin
  • Proteasome Endopeptidase Complex