Ganseerpel
Advisory Board, Senior Moderator
CTL epitopes for influenza A including the H5N1 bird flu; genome-, pathogen-, and HLA-wide screening . <?xml:namespace prefix = o ns = "urn:schemas-microsoft-com
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Vaccine <o></o>
doi:10.1016/j.vaccine.2006.12.038 <o></o>
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Mingjun Wanga, Kasper Lamberthb, Mikkel Harndahlb, Gustav R?derb, Anette Stryhnb, Mette V. Larsenc, Morten Nielsenc, Claus Lundegaardc, Sheila T. Tangc, Morten H. Dziegield, J?rgen Rosenkvistd, Anders E. Pedersena, S?ren Buusb, , , Mogens H. Claessona and Ole Lundc <o></o>
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aLaboratory of Cellular Immunology, Department of Medical Anatomy, The Panum Institute, University of Copenhagen, Blegdamsvej 3, 2200 Copenhagen N, Denmark<o></o>
bDivision of Experimental Immunology, Institute of Medical Microbiology and Immunology, The Panum Institute 18.3.12, University of Copenhagen, Blegdamsvej 3, 2200 Copenhagen N, Denmark<o></o>
cCenter for Biological Sequence Analysis, BioCentrum-DTU, Technical University of Denmark, Building 208, 2800 Lyngby, Denmark<o></o>
dH:S Blood Bank KI 2034, Copenhagen University Hospital, Blegdamsvej 9, 2100 Copenhagen ?, Denmark <o></o>
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Received 6 July 2006; revised 1 December 2006; accepted 12 December 2006. Available online 29 December 2006. <o></o>
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Abstract<o></o>
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-γ 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. <o></o>
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Keywords: Influenza A virus; Peptide; CTL epitope; Diagnostics; Vaccine <o></o>
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Corresponding author. Tel.: +45 3532 7885; fax: +45 3532 76
fficeffice" /><o></o><o
></o>Vaccine <o
></o>doi:10.1016/j.vaccine.2006.12.038 <o
></o><o
></o>Mingjun Wanga, Kasper Lamberthb, Mikkel Harndahlb, Gustav R?derb, Anette Stryhnb, Mette V. Larsenc, Morten Nielsenc, Claus Lundegaardc, Sheila T. Tangc, Morten H. Dziegield, J?rgen Rosenkvistd, Anders E. Pedersena, S?ren Buusb, , , Mogens H. Claessona and Ole Lundc <o
></o><o
></o>aLaboratory of Cellular Immunology, Department of Medical Anatomy, The Panum Institute, University of Copenhagen, Blegdamsvej 3, 2200 Copenhagen N, Denmark<o
></o>bDivision of Experimental Immunology, Institute of Medical Microbiology and Immunology, The Panum Institute 18.3.12, University of Copenhagen, Blegdamsvej 3, 2200 Copenhagen N, Denmark<o
></o>cCenter for Biological Sequence Analysis, BioCentrum-DTU, Technical University of Denmark, Building 208, 2800 Lyngby, Denmark<o
></o>dH:S Blood Bank KI 2034, Copenhagen University Hospital, Blegdamsvej 9, 2100 Copenhagen ?, Denmark <o
></o><o
></o>Received 6 July 2006; revised 1 December 2006; accepted 12 December 2006. Available online 29 December 2006. <o
></o><o
></o>Abstract<o
></o>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-γ 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. <o
></o><o
></o>Keywords: Influenza A virus; Peptide; CTL epitope; Diagnostics; Vaccine <o
></o><o
></o>Corresponding author. Tel.: +45 3532 7885; fax: +45 3532 76
