Clonal analysis of immunodominance and cross-reactivity of the CD4 T cell response to SARS-CoV-2
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Date
2021-06-18Type
- Journal Article
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Cited 48 times in
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Cited 54 times in
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Abstract
The identification of CD4+ T cell epitopes is instrumental for the design of subunit vaccines for broad protection against coronaviruses. Here, we demonstrate in COVID-19–recovered individuals a robust CD4+ T cell response to naturally processed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike (S) protein and nucleoprotein (N), including effector, helper, and memory T cells. By characterizing 2943 S-reactive T cell clones from 34 individuals, we found that the receptor-binding domain (RBD) is highly immunogenic and that 33% of RBD-reactive clones and 94% of individuals recognized a conserved immunodominant S346–S365 region comprising nested human leukocyte antigen DR (HLA-DR)– and HLA-DP–restricted epitopes. Using pre– and post–COVID-19 samples and S proteins from endemic coronaviruses, we identified cross-reactive T cells targeting multiple S protein sites. The immunodominant and cross-reactive epitopes identified can inform vaccination strategies to counteract emerging SARS-CoV-2 variants. Show more
Publication status
publishedExternal links
Journal / series
ScienceVolume
Pages / Article No.
Publisher
American Association for the Advancement of ScienceOrganisational unit
09604 - Sallusto, Federica / Sallusto, Federica
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Show all metadata
Citations
Cited 48 times in
Web of Science
Cited 54 times in
Scopus
ETH Bibliography
yes
Altmetrics