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

18 May 2020
Grifoni A, Weiskopf D, Ramirez SI, Mateus J, Dan JM, Moderbacher CR, Rawlings SA, Sutherland A, Premkumar L, Jadi RS, Marrama D, de Silva AM, Frazier A, Carlin A, Greenbaum JA, Peters B, Krammer F, Smith DM, Crotty S and Sette A


  • Measuring immunity to SARS-CoV-2 is key for understanding COVID19 and vaccine development
  • Epitope pools detect CD4⁺ and CD8⁺ T cells in 100 and 70% of convalescent COVID patients
  • T cell responses are focused not only on spike but also on M, N and other ORFs
  • T cell reactivity to SARS-CoV-2 epitopes is also detected in non-exposed individuals


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.