NetH2pan: A Computational Tool to Guide MHC peptide prediction on Murine Tumors

Christa I DeVette, Massimo Andreatta, Wilfried Bardet, Steven J Cate, Vanessa Isabell Jurtz, Kenneth W Jackson, Alana L Welm, Morten Nielsen, William H Hildebrand*

*Corresponding author for this work

    Research output: Contribution to journalJournal articleResearchpeer-review

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    Abstract

    With the advancement of personalized cancer immunotherapies, new tools are needed to identify tumor antigens and evaluate T-cell responses in model systems, specifically those that exhibit clinically relevant tumor progression. Key transgenic mouse models of breast cancer are generated and maintained on the FVB genetic background, and one such model is the mouse mammary tumor virus-polyomavirus middle T antigen (MMTV-PyMT) mouse - an immunocompetent transgenic mouse that exhibits spontaneous mammary tumor development and metastasis with high penetrance. Backcrossing the MMTV-PyMT mouse from the FVB strain onto a C57BL/6 genetic background, in order to leverage well-developed C57BL/6 immunological tools, results in delayed tumor development and variable metastatic phenotypes. Therefore, we initiated characterization of the FVB MHC Class I H-2q haplotype to establish useful immunological tools for evaluating antigen specificity in the murine FVB strain. Our study provides the first detailed molecular and immunoproteomic characterization of the FVB H-2q MHC Class I alleles, including >8500 unique peptide ligands, a multi-allele murine MHC peptide prediction tool, and in vivo validation of these data using MMTV-PyMT primary tumors. This work allows researchers to rapidly predict H-2 peptide ligands for immune testing, including, but not limited to, the MMTV-PyMT model for metastatic breast cancer.
    Original languageEnglish
    JournalCancer Immunology Research
    Volume6
    Issue number6
    Pages (from-to)636-644
    Number of pages8
    ISSN2326-6066
    DOIs
    Publication statusPublished - 2018

    Cite this

    DeVette, C. I., Andreatta, M., Bardet, W., Cate, S. J., Jurtz, V. I., Jackson, K. W., ... Hildebrand, W. H. (2018). NetH2pan: A Computational Tool to Guide MHC peptide prediction on Murine Tumors. Cancer Immunology Research, 6(6), 636-644. https://doi.org/10.1158/2326-6066.CIR-17-0298
    DeVette, Christa I ; Andreatta, Massimo ; Bardet, Wilfried ; Cate, Steven J ; Jurtz, Vanessa Isabell ; Jackson, Kenneth W ; Welm, Alana L ; Nielsen, Morten ; Hildebrand, William H. / NetH2pan: A Computational Tool to Guide MHC peptide prediction on Murine Tumors. In: Cancer Immunology Research. 2018 ; Vol. 6, No. 6. pp. 636-644.
    @article{26b3c0e31c614dafa9a18a01751b061f,
    title = "NetH2pan: A Computational Tool to Guide MHC peptide prediction on Murine Tumors",
    abstract = "With the advancement of personalized cancer immunotherapies, new tools are needed to identify tumor antigens and evaluate T-cell responses in model systems, specifically those that exhibit clinically relevant tumor progression. Key transgenic mouse models of breast cancer are generated and maintained on the FVB genetic background, and one such model is the mouse mammary tumor virus-polyomavirus middle T antigen (MMTV-PyMT) mouse - an immunocompetent transgenic mouse that exhibits spontaneous mammary tumor development and metastasis with high penetrance. Backcrossing the MMTV-PyMT mouse from the FVB strain onto a C57BL/6 genetic background, in order to leverage well-developed C57BL/6 immunological tools, results in delayed tumor development and variable metastatic phenotypes. Therefore, we initiated characterization of the FVB MHC Class I H-2q haplotype to establish useful immunological tools for evaluating antigen specificity in the murine FVB strain. Our study provides the first detailed molecular and immunoproteomic characterization of the FVB H-2q MHC Class I alleles, including >8500 unique peptide ligands, a multi-allele murine MHC peptide prediction tool, and in vivo validation of these data using MMTV-PyMT primary tumors. This work allows researchers to rapidly predict H-2 peptide ligands for immune testing, including, but not limited to, the MMTV-PyMT model for metastatic breast cancer.",
    author = "DeVette, {Christa I} and Massimo Andreatta and Wilfried Bardet and Cate, {Steven J} and Jurtz, {Vanessa Isabell} and Jackson, {Kenneth W} and Welm, {Alana L} and Morten Nielsen and Hildebrand, {William H}",
    year = "2018",
    doi = "10.1158/2326-6066.CIR-17-0298",
    language = "English",
    volume = "6",
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    DeVette, CI, Andreatta, M, Bardet, W, Cate, SJ, Jurtz, VI, Jackson, KW, Welm, AL, Nielsen, M & Hildebrand, WH 2018, 'NetH2pan: A Computational Tool to Guide MHC peptide prediction on Murine Tumors', Cancer Immunology Research, vol. 6, no. 6, pp. 636-644. https://doi.org/10.1158/2326-6066.CIR-17-0298

    NetH2pan: A Computational Tool to Guide MHC peptide prediction on Murine Tumors. / DeVette, Christa I; Andreatta, Massimo; Bardet, Wilfried; Cate, Steven J; Jurtz, Vanessa Isabell; Jackson, Kenneth W; Welm, Alana L; Nielsen, Morten; Hildebrand, William H.

    In: Cancer Immunology Research, Vol. 6, No. 6, 2018, p. 636-644.

    Research output: Contribution to journalJournal articleResearchpeer-review

    TY - JOUR

    T1 - NetH2pan: A Computational Tool to Guide MHC peptide prediction on Murine Tumors

    AU - DeVette, Christa I

    AU - Andreatta, Massimo

    AU - Bardet, Wilfried

    AU - Cate, Steven J

    AU - Jurtz, Vanessa Isabell

    AU - Jackson, Kenneth W

    AU - Welm, Alana L

    AU - Nielsen, Morten

    AU - Hildebrand, William H

    PY - 2018

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    N2 - With the advancement of personalized cancer immunotherapies, new tools are needed to identify tumor antigens and evaluate T-cell responses in model systems, specifically those that exhibit clinically relevant tumor progression. Key transgenic mouse models of breast cancer are generated and maintained on the FVB genetic background, and one such model is the mouse mammary tumor virus-polyomavirus middle T antigen (MMTV-PyMT) mouse - an immunocompetent transgenic mouse that exhibits spontaneous mammary tumor development and metastasis with high penetrance. Backcrossing the MMTV-PyMT mouse from the FVB strain onto a C57BL/6 genetic background, in order to leverage well-developed C57BL/6 immunological tools, results in delayed tumor development and variable metastatic phenotypes. Therefore, we initiated characterization of the FVB MHC Class I H-2q haplotype to establish useful immunological tools for evaluating antigen specificity in the murine FVB strain. Our study provides the first detailed molecular and immunoproteomic characterization of the FVB H-2q MHC Class I alleles, including >8500 unique peptide ligands, a multi-allele murine MHC peptide prediction tool, and in vivo validation of these data using MMTV-PyMT primary tumors. This work allows researchers to rapidly predict H-2 peptide ligands for immune testing, including, but not limited to, the MMTV-PyMT model for metastatic breast cancer.

    AB - With the advancement of personalized cancer immunotherapies, new tools are needed to identify tumor antigens and evaluate T-cell responses in model systems, specifically those that exhibit clinically relevant tumor progression. Key transgenic mouse models of breast cancer are generated and maintained on the FVB genetic background, and one such model is the mouse mammary tumor virus-polyomavirus middle T antigen (MMTV-PyMT) mouse - an immunocompetent transgenic mouse that exhibits spontaneous mammary tumor development and metastasis with high penetrance. Backcrossing the MMTV-PyMT mouse from the FVB strain onto a C57BL/6 genetic background, in order to leverage well-developed C57BL/6 immunological tools, results in delayed tumor development and variable metastatic phenotypes. Therefore, we initiated characterization of the FVB MHC Class I H-2q haplotype to establish useful immunological tools for evaluating antigen specificity in the murine FVB strain. Our study provides the first detailed molecular and immunoproteomic characterization of the FVB H-2q MHC Class I alleles, including >8500 unique peptide ligands, a multi-allele murine MHC peptide prediction tool, and in vivo validation of these data using MMTV-PyMT primary tumors. This work allows researchers to rapidly predict H-2 peptide ligands for immune testing, including, but not limited to, the MMTV-PyMT model for metastatic breast cancer.

    U2 - 10.1158/2326-6066.CIR-17-0298

    DO - 10.1158/2326-6066.CIR-17-0298

    M3 - Journal article

    C2 - 29615400

    VL - 6

    SP - 636

    EP - 644

    JO - Cancer Immunology Research

    JF - Cancer Immunology Research

    SN - 2326-6066

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    ER -