Simultaneous analysis of pMHC binding and reactivity unveils virus-specific CD8 T cell immunity to a concise epitope set

CD8 T cells provide immunity to virus infection through recognition of epitopes presented by peptide major histocompatibility complexes (pMHCs). To establish a concise panel of widely recognized T cell epitopes from common viruses, we combined analysis of TCR down-regulation upon stimulation with epitope-specific enumeration based on barcode-labeled pMHC multimers. We assess CD8 T cell binding and reactivity for 929 previously reported epitopes in the context of 1 of 25 HLA alleles representing 29 viruses. The prevalence and magnitude of CD8 T cell responses were evaluated in 48 donors and reported along with 137 frequently recognized virus epitopes, many of which were underrepresented in the public domain. Eighty-four percent of epitope-specific CD8 T cell populations demonstrated reactivity to peptide stimulation, which was associated with effector and long-term memory phenotypes. Conversely, nonreactive T cell populations were associated primarily with naive phenotypes. Our analysis provides a reference map of epitopes for characterizing CD8 T cell responses toward common human virus infections.