Mary Wilson
Well-known member
Published: 01 December 2022
https://doi.org/10.1038/s41590-022-01351-7
Emily X. C. Tye, Elizabeth Jinks, Tracey A. Haigh, Baksho Kaul, Prashant Patel, Helen M. Parry, Maddy L. Newby, Max Crispin, Nayandeep Kaur, Paul Moss, Samantha J. Drennan, Graham S. Taylor & Heather M. Long
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.
https://www.nature.com/articles/s41590-022-01351-7#citeas
https://doi.org/10.1038/s41590-022-01351-7
Emily X. C. Tye, Elizabeth Jinks, Tracey A. Haigh, Baksho Kaul, Prashant Patel, Helen M. Parry, Maddy L. Newby, Max Crispin, Nayandeep Kaur, Paul Moss, Samantha J. Drennan, Graham S. Taylor & Heather M. Long
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.
https://www.nature.com/articles/s41590-022-01351-7#citeas