open access publication

Article, 2024

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

Science Advances, ISSN 2375-2548, Volume 10, 15, Page eadm8951, 10.1126/sciadv.adm8951

Contributors

Kristensen, Nikolaj Pagh 0000-0002-5073-7153 [1] Dionisio, Edoardo [1] Bentzen, Amalie Kai Kai 0000-0002-5184-3054 [1] Tamhane, Tripti [1] Kemming, Janine Sophie 0000-0002-7967-9313 [1] Nos, Grigorii 0000-0002-8066-7424 [1] Voss, Lasse Frank 0000-0003-0904-6753 [1] Hansen, Ulla Kring 0000-0001-9668-8038 [1] Lauer, Georg Michael 0000-0002-9792-4271 [2] [3] Hadrup, Sine Reker 0000-0002-5937-4344 (Corresponding author) [1]

Affiliations

  1. [1] Technical University of Denmark
    2. [NORA names: DTU Technical University of Denmark; University; Denmark; Europe, EU; Nordic; OECD];
  2. [2] Harvard University
    3. [NORA names: United States; America, North; OECD];
  3. [3] Massachusetts General Hospital
    4. [NORA names: United States; America, North; OECD]

Abstract

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.

Keywords

CD8, CD8 T cell immunity, CD8 T cell populations, CD8 T cell responses, CD8 T cells, HLA, HLA alleles, T cell binding, T cell epitopes, T cell immunity, T cell populations, T cell responses, T cells, TCR down-regulation, alleles, analysis, associated with effector, binding, complex, context, domain, donor, down-regulation, effector, enumeration, epitopes, histocompatibility complex, human virus infections, immunity, immunity to virus infection, infection, long-term memory phenotype, magnitude, magnitude of CD8 T cell responses, major histocompatibility complex, mapping of epitopes, memory phenotype, multimers, naive phenotype, pMHC binding, peptide, peptide major histocompatibility complex, peptide stimulation, phenotype, population, prevalence, public domain, reactivity, recognition, recognition of epitopes, reference, reference map, response, simultaneous analysis, stimulation, virus, virus epitopes, virus infection

Funders

  • European Research Council
  • Lundbeck Foundation

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