Most viral peptides displayed by class I MHC on infected cells are immunogenic

Nathan P. Croft, Stewart A. Smith, Jana Pickering, John Sidney, Bjoern Peters, Pouya Faridi, Matthew J. Witney, Prince Sebastian, Inge E.A. Flesch, Sally L. Heading, Alessandro Sette, Nicole L. La Gruta, Anthony W. Purcell, David C. Tscharke

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CD8 + T cells are essential effectors in antiviral immunity, recognizing short virus-derived peptides presented by MHC class I (pMHCI) on the surface of infected cells. However, the fraction of viral pMHCI on infected cells that are immunogenic has not been shown for any virus. To approach this fundamental question, we used peptide sequencing by high-resolution mass spectrometry to identify more than 170 vaccinia virus pMHCI presented on infected mouse cells. Next, we screened each peptide for immunogenicity in multiple virus-infected mice, revealing a wide range of immu-nogenicities. A surprisingly high fraction (>80%) of pMHCI were immunogenic in at least one infected mouse, and nearly 40% were immunogenic across more than half of the mice screened. The high number of peptides found to be immunogenic and the distribution of responses across mice give us insight into the specificity of antiviral CD8 + T cell responses.

Original languageEnglish
Pages (from-to)3112-3117
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number8
Publication statusPublished - 19 Feb 2019


  • Antigen presentation
  • CD8 T cells
  • MHC class I
  • Vaccinia virus
  • Virus

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