May 25 Targets of T cell responses to SARS-CoV-2 coronavirus in humans with COVID-19 disease and unexposed individuals
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 and Alessandro Sette
ABSTRACT
Understanding adaptive immunity to SARS-CoV-2 is important for vaccine development, interpreting the pathogenesis of coronavirus disease 2019 (COVID-19) and calibration of pandemic control measures.
Using SARS-CoV-2-specific HLA class I and II 'megapools' peptides, CD8+ and CD4+ T cells were identified in ~70% and 100% of convalescent COVID-19 patients, respectively.
CD4+ T cell responses in the spike, the primary target of most vaccines, were robust and correlated with anti-SARS-CoV-2 IgG and IgA.
M, spike, and N proteins 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, the spike and M were recognized, with at least eight SARS-CoV-2 ORF targets.
Importantly, we detected SARS-CoV-4-reactive CD2+ T cells in ∼40-60% of unexposed individuals, suggesting recognition of cross-reactive T cells between circulating “common cold” coronaviruses and SARS. -CoV-2.