tetano
Editor, Senior Moderator
Immunity
. 2021 Apr 13;S1074-7613(21)00168-0.
doi: 10.1016/j.immuni.2021.04.006. Online ahead of print.
CD8 [SUP]+[/SUP] T cells specific for an immunodominant SARS-CoV-2 nucleocapsid epitope cross-react with selective seasonal coronaviruses
Katie E Lineburg[SUP] 1 [/SUP], Emma J Grant[SUP] 2 [/SUP], Srividhya Swaminathan[SUP] 3 [/SUP], Demetra S M Chatzileontiadou[SUP] 2 [/SUP], Christopher Szeto[SUP] 2 [/SUP], Hannah Sloane[SUP] 2 [/SUP], Archana Panikkar[SUP] 1 [/SUP], Jyothy Raju[SUP] 1 [/SUP], Pauline Crooks[SUP] 1 [/SUP], Sweera Rehan[SUP] 1 [/SUP], Andrea T Nguyen[SUP] 2 [/SUP], Lea Lekieffre[SUP] 1 [/SUP], Michelle A Neller[SUP] 1 [/SUP], Zhen Wei Marcus Tong[SUP] 4 [/SUP], Dhilshan Jayasinghe[SUP] 2 [/SUP], Keng Yih Chew[SUP] 4 [/SUP], Christian A Lobos[SUP] 2 [/SUP], Hanim Halim[SUP] 5 [/SUP], Jacqueline M Burrows[SUP] 1 [/SUP], Alan Riboldi-Tunnicliffe[SUP] 6 [/SUP], Weisan Chen[SUP] 7 [/SUP], Lloyd D'Orsogna[SUP] 8 [/SUP], Rajiv Khanna[SUP] 1 [/SUP], Kirsty R Short[SUP] 9 [/SUP], Corey Smith[SUP] 10 [/SUP], Stephanie Gras[SUP] 11 [/SUP]
Affiliations
Abstract
Efforts are being made worldwide to understand the immune response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for the coronavirus disease 2019 (COVID-19) pandemic, including the impact of T cell immunity and cross-recognition with seasonal coronaviruses. Screening of SARS-CoV-2 peptide pools revealed that the nucleocapsid (N) protein induced an immunodominant response in HLA-B7[SUP]+[/SUP] COVID-19-recovered individuals that was also detectable in unexposed donors. A single N-encoded epitope that was highly conserved across circulating coronaviruses drove this immunodominant response. In vitro peptide stimulation and crystal structure analyses revealed T cell-mediated cross-reactivity toward circulating OC43 and HKU-1 betacoronaviruses but not 229E or NL63 alphacoronaviruses because of different peptide conformations. T cell receptor (TCR) sequencing indicated that cross-reactivity was driven by private TCR repertoires with a bias for TRBV27 and a long CDR3? loop. Our findings demonstrate the basis of selective T cell cross-reactivity for an immunodominant SARS-CoV-2 epitope and its homologs from seasonal coronaviruses, suggesting long-lasting protective immunity.
Keywords: CD8(+) T cell; HLA; SARS-CoV-2; cross-reactivity; immune response; immunodominant epitope; seasonal coronaviruses.
. 2021 Apr 13;S1074-7613(21)00168-0.
doi: 10.1016/j.immuni.2021.04.006. Online ahead of print.
CD8 [SUP]+[/SUP] T cells specific for an immunodominant SARS-CoV-2 nucleocapsid epitope cross-react with selective seasonal coronaviruses
Katie E Lineburg[SUP] 1 [/SUP], Emma J Grant[SUP] 2 [/SUP], Srividhya Swaminathan[SUP] 3 [/SUP], Demetra S M Chatzileontiadou[SUP] 2 [/SUP], Christopher Szeto[SUP] 2 [/SUP], Hannah Sloane[SUP] 2 [/SUP], Archana Panikkar[SUP] 1 [/SUP], Jyothy Raju[SUP] 1 [/SUP], Pauline Crooks[SUP] 1 [/SUP], Sweera Rehan[SUP] 1 [/SUP], Andrea T Nguyen[SUP] 2 [/SUP], Lea Lekieffre[SUP] 1 [/SUP], Michelle A Neller[SUP] 1 [/SUP], Zhen Wei Marcus Tong[SUP] 4 [/SUP], Dhilshan Jayasinghe[SUP] 2 [/SUP], Keng Yih Chew[SUP] 4 [/SUP], Christian A Lobos[SUP] 2 [/SUP], Hanim Halim[SUP] 5 [/SUP], Jacqueline M Burrows[SUP] 1 [/SUP], Alan Riboldi-Tunnicliffe[SUP] 6 [/SUP], Weisan Chen[SUP] 7 [/SUP], Lloyd D'Orsogna[SUP] 8 [/SUP], Rajiv Khanna[SUP] 1 [/SUP], Kirsty R Short[SUP] 9 [/SUP], Corey Smith[SUP] 10 [/SUP], Stephanie Gras[SUP] 11 [/SUP]
Affiliations
- PMID: 33945786
- PMCID: PMC8043652
- DOI: 10.1016/j.immuni.2021.04.006
Abstract
Efforts are being made worldwide to understand the immune response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for the coronavirus disease 2019 (COVID-19) pandemic, including the impact of T cell immunity and cross-recognition with seasonal coronaviruses. Screening of SARS-CoV-2 peptide pools revealed that the nucleocapsid (N) protein induced an immunodominant response in HLA-B7[SUP]+[/SUP] COVID-19-recovered individuals that was also detectable in unexposed donors. A single N-encoded epitope that was highly conserved across circulating coronaviruses drove this immunodominant response. In vitro peptide stimulation and crystal structure analyses revealed T cell-mediated cross-reactivity toward circulating OC43 and HKU-1 betacoronaviruses but not 229E or NL63 alphacoronaviruses because of different peptide conformations. T cell receptor (TCR) sequencing indicated that cross-reactivity was driven by private TCR repertoires with a bias for TRBV27 and a long CDR3? loop. Our findings demonstrate the basis of selective T cell cross-reactivity for an immunodominant SARS-CoV-2 epitope and its homologs from seasonal coronaviruses, suggesting long-lasting protective immunity.
Keywords: CD8(+) T cell; HLA; SARS-CoV-2; cross-reactivity; immune response; immunodominant epitope; seasonal coronaviruses.