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

Autor: 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.
Jazyk: angličtina
Zdroj: Nature immunology [Nat Immunol] 2022 Dec; Vol. 23 (12), pp. 1726-1734. Date of Electronic Publication: 2022 Dec 01.
DOI: 10.1038/s41590-022-01351-7
Abstrakt: 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.
(© 2022. The Author(s), under exclusive licence to Springer Nature America, Inc.)
Databáze: MEDLINE
Externí odkaz: