Mutations in SARS-CoV-2 spike protein impair epitope-specific CD4+ T cell recognition

Emily Tye, Elizabeth Jinks, Tracey Haigh, Baksho Kaul, Prashant Patel, Helen Parry, Maddy Newby, Max Crispin, Nayandeep Kaur, Paul Moss, Samantha Drennan, Graham Taylor, Heather Long*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

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Abstract

CD4+ T cells are essential for protection against viruses, including SARS-CoV-2. The sensitivity of CD4+ T cells to mutations in SARS-CoV-2 variants of concern (VOCs) is poorly understood. Here, we isolated 159 SARS-CoV-2-specific CD4+ 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+ 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. Ten of the 17 epitopes located in the spike protein were mutated in VOCs and CD4+ 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+ T cells likely limits evasion by current VOCs. However, continued genomic surveillance is vital to identify new mutations able to evade CD4+ T cell immunity.
Original languageEnglish
Pages (from-to)1726–1734
Number of pages23
JournalNature Immunology
Volume23
DOIs
Publication statusPublished - 1 Dec 2022

Keywords

  • Immunity
  • SARS-CoV-2
  • CD4 T cells
  • variants of concern
  • coronavirus

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