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

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.

Highlights

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  Measuring immunity to SARS-CoV-2 is key for understanding COVID19 and vaccine development

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  Epitope pools detect CD4 ⁺ and CD8 ⁺ T cells in 100 and 70% of convalescent COVID patients

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  T cell responses are focused not only on spike but also on M, N and other ORFs

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  T cell reactivity to SARS-CoV-2 epitopes is also detected in non-exposed individuals

Abstract

An analysis of immune cell responses to SARS-CoV-2 from recovered patients identifies the regions of the virus that is targeted and also reveals cross-reactivity with other common circulating coronaviruses