title: CTL epitopes for influenza A including the H5N1 bird flu; genome-, pathogen-, and HLA-wide screening.
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.
authors.affiliation: Laboratory of Cellular Immunology, Department of Medical Anatomy, The Panum Institute, University of Copenhagen, Blegdamsvej 3, 2200 Copenhagen N, Denmark.
authors.forename: Mingjun
authors.initials: M
authors.lastname: Wang
authors.forename: Kasper
authors.initials: K
authors.lastname: Lamberth
authors.forename: Mikkel
authors.initials: M
authors.lastname: Harndahl
authors.forename: Gustav
authors.initials: G
authors.lastname: Røder
authors.forename: Anette
authors.initials: A
authors.lastname: Stryhn
authors.forename: Mette V
authors.initials: MV
authors.lastname: Larsen
authors.forename: Morten
authors.initials: M
authors.lastname: Nielsen
authors.forename: Claus
authors.initials: C
authors.lastname: Lundegaard
authors.forename: Sheila T
authors.initials: ST
authors.lastname: Tang
authors.forename: Morten H
authors.initials: MH
authors.lastname: Dziegiel
authors.forename: Jørgen
authors.initials: J
authors.lastname: Rosenkvist
authors.forename: Anders E
authors.initials: AE
authors.lastname: Pedersen
authors.forename: Søren
authors.initials: S
authors.lastname: Buus
authors.forename: Mogens H
authors.initials: MH
authors.lastname: Claesson
authors.forename: Ole
authors.initials: O
authors.lastname: Lund
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D001717:Birds; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D005260:Female; D005820:Genetic Testing; D016679:Genome, Viral; D015234:HLA-A Antigens / Q000276:immunology*; D015235:HLA-B Antigens / Q000276:immunology*; D006801:Humans; D053124:Influenza A Virus, H5N1 Subtype / Q000235:genetics / Q000276:immunology*; D009980:Influenza A virus / Q000235:genetics / Q000276:immunology*; D005585:Influenza in Birds / Q000821:virology; D007251:Influenza, Human / Q000097:blood / Q000276:immunology* / Q000821:virology; D008297:Male; D026901:Membrane Transport Proteins / Q000276:immunology / Q000378:metabolism; D008875:Middle Aged; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000821:virology
chemical_list: D018984:Epitopes, T-Lymphocyte; D015234:HLA-A Antigens; D015235:HLA-B Antigens; D026901:Membrane Transport Proteins; C107762:tapasin; D046988:Proteasome Endopeptidase Complex