Identification of CD8(+) T Cell Epitopes in the West Nile Virus Polyprotein by Reverse-Immunology Using NetCTL

Mette Voldby Larsen, A. Lelic, R. Parsons, Morten Nielsen, I. Hoof, K. Lamberth, M.B. Loeb, S. Buus, J. Bramson, Ole Lund

    Research output: Contribution to journalJournal articleResearchpeer-review

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    Abstract

    Background: West Nile virus (WNV) is a growing threat to public health and a greater understanding of the immune response raised against WNV is important for the development of prophylactic and therapeutic strategies. Methodology/Principal Findings: In a reverse-immunology approach, we used bioinformatics methods to predict WNV-specific CD8(+) T cell epitopes and selected a set of peptides that constitutes maximum coverage of 20 fully-sequenced WNV strains. We then tested these putative epitopes for cellular reactivity in a cohort of WNV-infected patients. We identified 26 new CD8(+) T cell epitopes, which we propose are restricted by 11 different HLA class I alleles. Aiming for optimal coverage of human populations, we suggest that 11 of these new WNV epitopes would be sufficient to cover from 48% to 93% of ethnic populations in various areas of the World. Conclusions/Significance: The 26 identified CD8(+) T cell epitopes contribute to our knowledge of the immune response against WNV infection and greatly extend the list of known WNV CD8(+) T cell epitopes. A polytope incorporating these and other epitopes could possibly serve as the basis for a WNV vaccine.
    Original languageEnglish
    JournalP L o S One
    Volume5
    Issue number9
    ISSN1932-6203
    DOIs
    Publication statusPublished - 2010

    Bibliographical note

    This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

    Cite this

    Larsen, Mette Voldby ; Lelic, A. ; Parsons, R. ; Nielsen, Morten ; Hoof, I. ; Lamberth, K. ; Loeb, M.B. ; Buus, S. ; Bramson, J. ; Lund, Ole. / Identification of CD8(+) T Cell Epitopes in the West Nile Virus Polyprotein by Reverse-Immunology Using NetCTL. In: P L o S One. 2010 ; Vol. 5, No. 9.
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    title = "Identification of CD8(+) T Cell Epitopes in the West Nile Virus Polyprotein by Reverse-Immunology Using NetCTL",
    abstract = "Background: West Nile virus (WNV) is a growing threat to public health and a greater understanding of the immune response raised against WNV is important for the development of prophylactic and therapeutic strategies. Methodology/Principal Findings: In a reverse-immunology approach, we used bioinformatics methods to predict WNV-specific CD8(+) T cell epitopes and selected a set of peptides that constitutes maximum coverage of 20 fully-sequenced WNV strains. We then tested these putative epitopes for cellular reactivity in a cohort of WNV-infected patients. We identified 26 new CD8(+) T cell epitopes, which we propose are restricted by 11 different HLA class I alleles. Aiming for optimal coverage of human populations, we suggest that 11 of these new WNV epitopes would be sufficient to cover from 48{\%} to 93{\%} of ethnic populations in various areas of the World. Conclusions/Significance: The 26 identified CD8(+) T cell epitopes contribute to our knowledge of the immune response against WNV infection and greatly extend the list of known WNV CD8(+) T cell epitopes. A polytope incorporating these and other epitopes could possibly serve as the basis for a WNV vaccine.",
    author = "Larsen, {Mette Voldby} and A. Lelic and R. Parsons and Morten Nielsen and I. Hoof and K. Lamberth and M.B. Loeb and S. Buus and J. Bramson and Ole Lund",
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    Identification of CD8(+) T Cell Epitopes in the West Nile Virus Polyprotein by Reverse-Immunology Using NetCTL. / Larsen, Mette Voldby; Lelic, A.; Parsons, R.; Nielsen, Morten; Hoof, I.; Lamberth, K.; Loeb, M.B.; Buus, S.; Bramson, J.; Lund, Ole.

    In: P L o S One, Vol. 5, No. 9, 2010.

    Research output: Contribution to journalJournal articleResearchpeer-review

    TY - JOUR

    T1 - Identification of CD8(+) T Cell Epitopes in the West Nile Virus Polyprotein by Reverse-Immunology Using NetCTL

    AU - Larsen, Mette Voldby

    AU - Lelic, A.

    AU - Parsons, R.

    AU - Nielsen, Morten

    AU - Hoof, I.

    AU - Lamberth, K.

    AU - Loeb, M.B.

    AU - Buus, S.

    AU - Bramson, J.

    AU - Lund, Ole

    N1 - This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

    PY - 2010

    Y1 - 2010

    N2 - Background: West Nile virus (WNV) is a growing threat to public health and a greater understanding of the immune response raised against WNV is important for the development of prophylactic and therapeutic strategies. Methodology/Principal Findings: In a reverse-immunology approach, we used bioinformatics methods to predict WNV-specific CD8(+) T cell epitopes and selected a set of peptides that constitutes maximum coverage of 20 fully-sequenced WNV strains. We then tested these putative epitopes for cellular reactivity in a cohort of WNV-infected patients. We identified 26 new CD8(+) T cell epitopes, which we propose are restricted by 11 different HLA class I alleles. Aiming for optimal coverage of human populations, we suggest that 11 of these new WNV epitopes would be sufficient to cover from 48% to 93% of ethnic populations in various areas of the World. Conclusions/Significance: The 26 identified CD8(+) T cell epitopes contribute to our knowledge of the immune response against WNV infection and greatly extend the list of known WNV CD8(+) T cell epitopes. A polytope incorporating these and other epitopes could possibly serve as the basis for a WNV vaccine.

    AB - Background: West Nile virus (WNV) is a growing threat to public health and a greater understanding of the immune response raised against WNV is important for the development of prophylactic and therapeutic strategies. Methodology/Principal Findings: In a reverse-immunology approach, we used bioinformatics methods to predict WNV-specific CD8(+) T cell epitopes and selected a set of peptides that constitutes maximum coverage of 20 fully-sequenced WNV strains. We then tested these putative epitopes for cellular reactivity in a cohort of WNV-infected patients. We identified 26 new CD8(+) T cell epitopes, which we propose are restricted by 11 different HLA class I alleles. Aiming for optimal coverage of human populations, we suggest that 11 of these new WNV epitopes would be sufficient to cover from 48% to 93% of ethnic populations in various areas of the World. Conclusions/Significance: The 26 identified CD8(+) T cell epitopes contribute to our knowledge of the immune response against WNV infection and greatly extend the list of known WNV CD8(+) T cell epitopes. A polytope incorporating these and other epitopes could possibly serve as the basis for a WNV vaccine.

    U2 - 10.1371/journal.pone.0012697

    DO - 10.1371/journal.pone.0012697

    M3 - Journal article

    VL - 5

    JO - P L o S One

    JF - P L o S One

    SN - 1932-6203

    IS - 9

    ER -