SARS-CoV-2-specific T cell immunity in cases of COVID-19 and SARS, and uninfected controls.
2020 Jul 15
a month ago
Publication Type
Journal Article
2020-Jul-15 / :
Le Bert N 1, Tan AT 1, Kunasegaran K 1, Tham CYL 1, Hafezi M 1, Chia A 1, Chng MHY 1, Lin M 1, 2, Tan N 1, Linster M 1, Chia WN 1, Chen MI 3, Wang LF 1, Ooi EE 1, Kalimuddin S 4, Tambyah PA 5, 6, Low JG 1, 4, Tan YJ 2, 7, Bertoletti A 8, 9
  • 2. Institute of Molecular and Cell Biology (IMCB), A*STAR, Singapore, Singapore.
  • 3. National Center of Infectious Diseases, Singapore, Singapore.
  • 4. Department of Infectious Diseases, Singapore General Hospital, Singapore, Singapore.
  • 5. Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
  • 6. Division of Infectious Disease, University Medicine Cluster, National University Hospital, Singapore, Singapore.
  • 7. Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
  • 8. Emerging Infectious Diseases Program, Duke-NUS Medical School, Singapore, Singapore. [email protected]
  • 9. Singapore Immunology Network, A*STAR, Singapore, Singapore. [email protected]
Memory T cells induced by previous pathogens can shape the susceptibility to, and clinical severity of, subsequent infections1. Little is known about the presence of pre-existing memory T cells in humans with the potential to recognize SARS-CoV-2. Here, we first studied T cell responses to structural (nucleocapsid protein, NP) and non-structural (NSP-7 and NSP13 of ORF1) regions of SARS-CoV-2 in COVID-19 convalescents (n=36). In all of them we demonstrated the presence of CD4 and CD8 T cells recognizing multiple regions of the NP protein. We then showed that SARS-recovered patients (n=23) still possess long-lasting memory T cells reactive to SARS-NP 17 years after the 2003 outbreak, which displayed robust cross-reactivity to SARS-CoV-2 NP. Surprisingly, we also frequently detected SARS-CoV-2 specific T cells in individuals with no history of SARS, COVID-19 or contact with SARS/COVID-19 patients (n=37). SARS-CoV-2 T cells in uninfected donors exhibited a different pattern of immunodominance, frequently targeting the ORF-1-coded proteins NSP7 and 13 as well as the NP structural protein. Epitope characterization of NSP7-specific T cells showed recognition of protein fragments with low homology to "common cold" human coronaviruses but conserved amongst animal betacoranaviruses. Thus, infection with betacoronaviruses induces multispecific and long-lasting T cell immunity to the structural protein NP. Understanding how pre-existing NP- and ORF-1-specific T cells present in the general population impact susceptibility and pathogenesis of SARS-CoV-2 infection is of paramount importance for the management of the current COVID-19 pandemic.

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