CTL epitopes for influenza A including the H5N1 bird flu; genome-, pathogen-, and HLA-wide screening.
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.
Wang
Mingjun
M
Laboratory of Cellular Immunology, Department of Medical Anatomy, The Panum Institute, University of Copenhagen, Blegdamsvej 3, 2200 Copenhagen N, Denmark.
Lamberth
Kasper
K
Harndahl
Mikkel
M
Røder
Gustav
G
Stryhn
Anette
A
Larsen
Mette V
MV
Nielsen
Morten
M
Lundegaard
Claus
C
Tang
Sheila T
ST
Dziegiel
Morten H
MH
Rosenkvist
Jørgen
J
Pedersen
Anders E
AE
Buus
Søren
S
Claesson
Mogens H
MH
Lund
Ole
O
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
D018984:Epitopes, T-Lymphocyte; D015234:HLA-A Antigens; D015235:HLA-B Antigens; D026901:Membrane Transport Proteins; C107762:tapasin; D046988:Proteasome Endopeptidase Complex