tetano
Editor, Senior Moderator
Nat Immunol
. 2022 Dec 1.
doi: 10.1038/s41590-022-01351-7. Online ahead of print.
Mutations in SARS-CoV-2 spike protein impair epitope-specific CD4[SUP]+[/SUP] T cell recognition
Emily X C Tye[SUP] 1 [/SUP], Elizabeth Jinks[SUP] 1 [/SUP], Tracey A Haigh[SUP] 1 [/SUP], Baksho Kaul[SUP] 1 [/SUP], Prashant Patel[SUP] 2 [/SUP], Helen M Parry[SUP] 1 [/SUP], Maddy L Newby[SUP] 3 [/SUP], Max Crispin[SUP] 3 [/SUP], Nayandeep Kaur[SUP] 1 [/SUP], Paul Moss[SUP] 1 [/SUP], Samantha J Drennan[SUP] 1 [/SUP], Graham S Taylor[SUP] 1 [/SUP], Heather M Long[SUP] 4 [/SUP]
Affiliations
Abstract
CD4[SUP]+[/SUP] T cells are essential for protection against viruses, including SARS-CoV-2. The sensitivity of CD4[SUP]+[/SUP] T cells to mutations in SARS-CoV-2 variants of concern (VOCs) is poorly understood. Here, we isolated 159 SARS-CoV-2-specific CD4[SUP]+[/SUP] T cell clones from healthcare workers previously infected with wild-type SARS-CoV-2 (D614G) and defined 21 epitopes in spike, membrane and nucleoprotein. Lack of CD4[SUP]+[/SUP] T cell cross-reactivity between SARS-CoV-2 and endemic beta-coronaviruses suggested these responses arose from naïve rather than pre-existing cross-reactive coronavirus-specific T cells. Of the 17 epitopes located in the spike protein, 10 were mutated in VOCs and CD4[SUP]+[/SUP] T cell clone recognition of 7 of them was impaired, including 3 of the 4 epitopes mutated in omicron. Our results indicated that broad targeting of epitopes by CD4[SUP]+[/SUP] T cells likely limits evasion by current VOCs. However, continued genomic surveillance is vital to identify new mutations able to evade CD4[SUP]+[/SUP] T cell immunity.
. 2022 Dec 1.
doi: 10.1038/s41590-022-01351-7. Online ahead of print.
Mutations in SARS-CoV-2 spike protein impair epitope-specific CD4[SUP]+[/SUP] T cell recognition
Emily X C Tye[SUP] 1 [/SUP], Elizabeth Jinks[SUP] 1 [/SUP], Tracey A Haigh[SUP] 1 [/SUP], Baksho Kaul[SUP] 1 [/SUP], Prashant Patel[SUP] 2 [/SUP], Helen M Parry[SUP] 1 [/SUP], Maddy L Newby[SUP] 3 [/SUP], Max Crispin[SUP] 3 [/SUP], Nayandeep Kaur[SUP] 1 [/SUP], Paul Moss[SUP] 1 [/SUP], Samantha J Drennan[SUP] 1 [/SUP], Graham S Taylor[SUP] 1 [/SUP], Heather M Long[SUP] 4 [/SUP]
Affiliations
- PMID: 36456735
- DOI: 10.1038/s41590-022-01351-7
Abstract
CD4[SUP]+[/SUP] T cells are essential for protection against viruses, including SARS-CoV-2. The sensitivity of CD4[SUP]+[/SUP] T cells to mutations in SARS-CoV-2 variants of concern (VOCs) is poorly understood. Here, we isolated 159 SARS-CoV-2-specific CD4[SUP]+[/SUP] T cell clones from healthcare workers previously infected with wild-type SARS-CoV-2 (D614G) and defined 21 epitopes in spike, membrane and nucleoprotein. Lack of CD4[SUP]+[/SUP] T cell cross-reactivity between SARS-CoV-2 and endemic beta-coronaviruses suggested these responses arose from naïve rather than pre-existing cross-reactive coronavirus-specific T cells. Of the 17 epitopes located in the spike protein, 10 were mutated in VOCs and CD4[SUP]+[/SUP] T cell clone recognition of 7 of them was impaired, including 3 of the 4 epitopes mutated in omicron. Our results indicated that broad targeting of epitopes by CD4[SUP]+[/SUP] T cells likely limits evasion by current VOCs. However, continued genomic surveillance is vital to identify new mutations able to evade CD4[SUP]+[/SUP] T cell immunity.