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Mutations in SARS-CoV-2 spike protein impair epitope-specific CD4+ T cell recognition.
Tye, Emily X C; Jinks, Elizabeth; Haigh, Tracey A; Kaul, Baksho; Patel, Prashant; Parry, Helen M; Newby, Maddy L; Crispin, Max; Kaur, Nayandeep; Moss, Paul; Drennan, Samantha J; Taylor, Graham S; Long, Heather M.
  • Tye EXC; Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, UK.
  • Jinks E; Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, UK.
  • Haigh TA; Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, UK.
  • Kaul B; Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, UK.
  • Patel P; Institute of Cancer and Genomics, University of Birmingham, Birmingham, UK.
  • Parry HM; Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, UK.
  • Newby ML; School of Biological Sciences, University of Southampton, Southampton, UK.
  • Crispin M; School of Biological Sciences, University of Southampton, Southampton, UK.
  • Kaur N; Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, UK.
  • Moss P; Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, UK.
  • Drennan SJ; Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, UK.
  • Taylor GS; Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, UK.
  • Long HM; Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, UK. h.m.long@bham.ac.uk.
Nat Immunol ; 2022 Dec 01.
Article in English | MEDLINE | ID: covidwho-2284754
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. Of the 17 epitopes located in the spike protein, 10 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.

Full text: Available Collection: International databases Database: MEDLINE Type of study: Randomized controlled trials Topics: Variants Language: English Journal subject: Allergy and Immunology Year: 2022 Document Type: Article Affiliation country: S41590-022-01351-7

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Full text: Available Collection: International databases Database: MEDLINE Type of study: Randomized controlled trials Topics: Variants Language: English Journal subject: Allergy and Immunology Year: 2022 Document Type: Article Affiliation country: S41590-022-01351-7