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Targets of T Cell Responses to SARS-CoV-2 Coronavirus in Humans with COVID-19 Disease and Unexposed Individuals.

  • Author(s): Grifoni, Alba
  • Weiskopf, Daniela
  • Ramirez, Sydney I
  • Mateus, Jose
  • Dan, Jennifer M
  • Moderbacher, Carolyn Rydyznski
  • Rawlings, Stephen A
  • Sutherland, Aaron
  • Premkumar, Lakshmanane
  • Jadi, Ramesh S
  • Marrama, Daniel
  • de Silva, Aravinda M
  • Frazier, April
  • Carlin, Aaron F
  • Greenbaum, Jason A
  • Peters, Bjoern
  • Krammer, Florian
  • Smith, Davey M
  • Crotty, Shane
  • Sette, Alessandro
  • et al.

Understanding adaptive immunity to SARS-CoV-2 is important for vaccine development, interpreting coronavirus disease 2019 (COVID-19) pathogenesis, and calibration of pandemic control measures. Using HLA class I and II predicted peptide "megapools," circulating SARS-CoV-2-specific CD8+ and CD4+ T cells were identified in ∼70% and 100% of COVID-19 convalescent patients, respectively. CD4+ T cell responses to spike, the main target of most vaccine efforts, were robust and correlated with the magnitude of the anti-SARS-CoV-2 IgG and IgA titers. The M, spike, and N proteins each accounted for 11%-27% of the total CD4+ response, with additional responses commonly targeting nsp3, nsp4, ORF3a, and ORF8, among others. For CD8+ T cells, spike and M were recognized, with at least eight SARS-CoV-2 ORFs targeted. Importantly, we detected SARS-CoV-2-reactive CD4+ T cells in ∼40%-60% of unexposed individuals, suggesting cross-reactive T cell recognition between circulating "common cold" coronaviruses and SARS-CoV-2.

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