tetano
Editor, Senior Moderator
Nature
. 2020 Jul 15.
doi: 10.1038/s41586-020-2550-z. Online ahead of print.
SARS-CoV-2-specific T cell immunity in cases of COVID-19 and SARS, and uninfected controls
Nina Le Bert[SUP] 1 [/SUP], Anthony T Tan[SUP] 1 [/SUP], Kamini Kunasegaran[SUP] 1 [/SUP], Christine Y L Tham[SUP] 1 [/SUP], Morteza Hafezi[SUP] 1 [/SUP], Adeline Chia[SUP] 1 [/SUP], Melissa Hui Yen Chng[SUP] 1 [/SUP], Meiyin Lin[SUP] 1 2 [/SUP], Nicole Tan[SUP] 1 [/SUP], Martin Linster[SUP] 1 [/SUP], Wan Ni Chia[SUP] 1 [/SUP], Mark I-Cheng Chen[SUP] 3 [/SUP], Lin-Fa Wang[SUP] 1 [/SUP], Eng Eong Ooi[SUP] 1 [/SUP], Shirin Kalimuddin[SUP] 4 [/SUP], Paul Anantharajal Tambyah[SUP] 5 6 [/SUP], Jenny Guek-Hong Low[SUP] 1 4 [/SUP], Yee-Joo Tan[SUP] 2 7 [/SUP], Antonio Bertoletti[SUP] 8 9 [/SUP]
Affiliations
Abstract
Memory T cells induced by previous pathogens can shape the susceptibility to, and clinical severity of, subsequent infections[SUP]1[/SUP]. 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.
. 2020 Jul 15.
doi: 10.1038/s41586-020-2550-z. Online ahead of print.
SARS-CoV-2-specific T cell immunity in cases of COVID-19 and SARS, and uninfected controls
Nina Le Bert[SUP] 1 [/SUP], Anthony T Tan[SUP] 1 [/SUP], Kamini Kunasegaran[SUP] 1 [/SUP], Christine Y L Tham[SUP] 1 [/SUP], Morteza Hafezi[SUP] 1 [/SUP], Adeline Chia[SUP] 1 [/SUP], Melissa Hui Yen Chng[SUP] 1 [/SUP], Meiyin Lin[SUP] 1 2 [/SUP], Nicole Tan[SUP] 1 [/SUP], Martin Linster[SUP] 1 [/SUP], Wan Ni Chia[SUP] 1 [/SUP], Mark I-Cheng Chen[SUP] 3 [/SUP], Lin-Fa Wang[SUP] 1 [/SUP], Eng Eong Ooi[SUP] 1 [/SUP], Shirin Kalimuddin[SUP] 4 [/SUP], Paul Anantharajal Tambyah[SUP] 5 6 [/SUP], Jenny Guek-Hong Low[SUP] 1 4 [/SUP], Yee-Joo Tan[SUP] 2 7 [/SUP], Antonio Bertoletti[SUP] 8 9 [/SUP]
Affiliations
- PMID: 32668444
- DOI: 10.1038/s41586-020-2550-z
Abstract
Memory T cells induced by previous pathogens can shape the susceptibility to, and clinical severity of, subsequent infections[SUP]1[/SUP]. 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.