[PDF][PDF] Targets of T cell responses to SARS-CoV-2 coronavirus in humans with COVID-19 disease and unexposed individuals

A Grifoni, D Weiskopf, SI Ramirez, J Mateus, JM Dan… - Cell, 2020 - cell.com
Cell, 2020cell.com
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 …
Summary
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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