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Selective and cross-reactive SARS-CoV-2 T cell epitopes in unexposed humans.

  • Mateus, Jose
  • Grifoni, Alba
  • Tarke, Alison
  • Sidney, John
  • Ramirez, Sydney I
  • Dan, Jennifer M
  • Burger, Zoe C
  • Rawlings, Stephen A
  • Smith, Davey M
  • Phillips, Elizabeth
  • Mallal, Simon
  • Lammers, Marshall
  • Rubiro, Paul
  • Quiambao, Lorenzo
  • Sutherland, Aaron
  • Yu, Esther Dawen
  • da Silva Antunes, Ricardo
  • Greenbaum, Jason
  • Frazier, April
  • Markmann, Alena J
  • And 6 more
Publication Date
Oct 01, 2020
eScholarship - University of California
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Many unknowns exist about human immune responses to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus. SARS-CoV-2-reactive CD4+ T cells have been reported in unexposed individuals, suggesting preexisting cross-reactive T cell memory in 20 to 50% of people. However, the source of those T cells has been speculative. Using human blood samples derived before the SARS-CoV-2 virus was discovered in 2019, we mapped 142 T cell epitopes across the SARS-CoV-2 genome to facilitate precise interrogation of the SARS-CoV-2-specific CD4+ T cell repertoire. We demonstrate a range of preexisting memory CD4+ T cells that are cross-reactive with comparable affinity to SARS-CoV-2 and the common cold coronaviruses human coronavirus (HCoV)-OC43, HCoV-229E, HCoV-NL63, and HCoV-HKU1. Thus, variegated T cell memory to coronaviruses that cause the common cold may underlie at least some of the extensive heterogeneity observed in coronavirus disease 2019 (COVID-19) disease.

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