Updated publication reference for PubMed record(s): 30718433. CD8+ T cells are essential effectors in anti-viral immunity, recognising 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 nearly 200 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 at least one infected animal and around half of these were dominant, which we define as being immunogenic across more than half of the mice screened. The high number of peptides found to be immunogenic and the variability in immunogenicity across mice give us new insight into the specificity of anti-viral CD8+ T cell responses.