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

Proc Natl Acad Sci U S A. 2019 Feb 19;116(8):3112-3117. doi: 10.1073/pnas.1815239116. Epub 2019 Feb 4.


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 immunogenicities. 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.

Keywords: CD8+ T cells; MHC class I; antigen presentation; vaccinia virus; virus.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibody Formation / genetics
  • Antibody Formation / immunology*
  • Antigen Presentation / genetics
  • Antigen Presentation / immunology
  • CD8-Positive T-Lymphocytes / immunology*
  • Histocompatibility Antigens Class I / genetics
  • Histocompatibility Antigens Class I / immunology*
  • Humans
  • Immunity, Cellular / genetics
  • Immunogenetic Phenomena / genetics
  • Lymphocyte Activation / immunology
  • Mice
  • Peptides / genetics
  • Peptides / immunology*
  • T-Lymphocytes, Cytotoxic / immunology
  • Vaccinia virus / immunology
  • Vaccinia virus / pathogenicity


  • Histocompatibility Antigens Class I
  • Peptides