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

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.

Cell Published:May 14, 2020DOI:https://doi.org/10.1016/j.cell.2020.05.015