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

Nicole Frahm, Daniel E. Kaufmann, Karina Yusim, Mark Muldoon, Can Kesmir, Caitlyn H. Linde, Will Fischer, Todd M. Allen, Bin Li, Ben H. McMahon, Kellie L. Faircloth, Hannah S. Hewitt, Elizabeth W. Mackey, Toshiyuki Miura, Ashok Khatri, Steven Wolinsky, Andrew McMichael, Robert K. Funkhouser, Bruce D. Walker, Christian Brander*Bette T. Korber

*Corresponding author for this work

Research output: Contribution to journalArticle

32 Scopus citations

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-γ 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 (US)
Pages (from-to)6638-6650
Number of pages13
JournalJournal of Immunology
Volume179
Issue number10
DOIs
StatePublished - Nov 15 2007

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Frahm, N., Kaufmann, D. E., Yusim, K., Muldoon, M., Kesmir, C., Linde, C. H., Fischer, W., Allen, T. M., Li, B., McMahon, B. H., Faircloth, K. L., Hewitt, H. S., Mackey, E. W., Miura, T., Khatri, A., Wolinsky, S., McMichael, A., Funkhouser, R. K., Walker, B. D., ... Korber, B. T. (2007). Increased sequence diversity coverage improves detection of HIV-specific T cell responses. Journal of Immunology, 179(10), 6638-6650. https://doi.org/10.4049/jimmunol.179.10.6638