Increased sequence diversity coverage improves detection of HIV-Specific T cell responses

N. Frahm, D.E. Kaufmann, K. Yusim, M. Muldoon, Can Kesmir, C.H. Linde, W. Fischer, T.M. Allen, B. Li, B.H. McMahon, K.L. Faircloth, H.S. Hewitt, E.W. Mackey, T. Miura, A. Khatri, S. Wolinsky, A. McMichael, R.K. Funkhouser, B.D. Walker, C. BranderB.T. Korber

    Research output: Contribution to journalJournal articleResearchpeer-review

    Abstract

    The accurate identification of HIV-specific T cell responses is important for determining the relationship between immune response, viral control, and disease progression. HIV-specific immune responses are usually measured using peptide sets based on consensus sequences, which frequently miss responses to regions where test set and infecting virus differ. In this study, we report the design of a peptide test set with significantly increased coverage of HIV sequence diversity by including alternative amino acids at variable positions during the peptide synthesis step. In an IFN-gamma ELISpot assay, these "toggled" peptides detected HIV-specific CD4(+) and CD8(+) T cell responses of significantly higher breadth and magnitude than matched consensus peptides. The observed increases were explained by a closer match of the toggled peptides to the autologous viral sequence. Toggled peptides therefore afford a cost-effective and significantly more complete view of the host immune response to HIV and are directly applicable to other variable pathogens.
    Original languageEnglish
    JournalJournal of Immunology
    Volume179
    Issue number10
    Pages (from-to)6638-6650
    ISSN0022-1767
    Publication statusPublished - 2007

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