Identification of conserved SARS-CoV-2 spike epitopes that expand public cTfh clonotypes in mild COVID-19 patients.
Journal
The Journal of experimental medicine
ISSN: 1540-9538
Titre abrégé: J Exp Med
Pays: United States
ID NLM: 2985109R
Informations de publication
Date de publication:
06 12 2021
06 12 2021
Historique:
received:
18
06
2021
revised:
21
08
2021
accepted:
28
09
2021
entrez:
14
10
2021
pubmed:
15
10
2021
medline:
26
10
2021
Statut:
ppublish
Résumé
Adaptive immunity is a fundamental component in controlling COVID-19. In this process, follicular helper T (Tfh) cells are a subset of CD4+ T cells that mediate the production of protective antibodies; however, the SARS-CoV-2 epitopes activating Tfh cells are not well characterized. Here, we identified and crystallized TCRs of public circulating Tfh (cTfh) clonotypes that are expanded in patients who have recovered from mild symptoms. These public clonotypes recognized the SARS-CoV-2 spike (S) epitopes conserved across emerging variants. The epitope of the most prevalent cTfh clonotype, S864-882, was presented by multiple HLAs and activated T cells in most healthy donors, suggesting that this S region is a universal T cell epitope useful for booster antigen. SARS-CoV-2-specific public cTfh clonotypes also cross-reacted with specific commensal bacteria. In this study, we identified conserved SARS-CoV-2 S epitopes that activate public cTfh clonotypes associated with mild symptoms.
Identifiants
pubmed: 34647971
pii: 212701
doi: 10.1084/jem.20211327
pmc: PMC8641254
pii:
doi:
Substances chimiques
Antibodies, Viral
0
Epitopes, T-Lymphocyte
0
HLA Antigens
0
Spike Glycoprotein, Coronavirus
0
spike protein, SARS-CoV-2
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Japan Agency for Medical Research and Development
ID : 20fk0108265
Organisme : Japan Society for the Promotion of Science
ID : JP18H05279
Organisme : Kansai Economic Federation
Organisme : Mitsubishi Foundation
Organisme : AnGes
Organisme : Daicel
Organisme : FunPep
Informations de copyright
© 2021 Lu et al.
Déclaration de conflit d'intérêts
Disclosures: N. Sax reported personal fees from KOTAI Biotechnologies, Inc. outside the submitted work; in addition, N. Sax had a patent to "follicular helper T cells specific for SARS-CoV-2 virus" pending and a patent to "novel medical technology using follicular T cells" pending. H. Nakagami reported that the Department of Health Development and Medicine is an endowed department supported by Anges, Daicel, and Funpep. K. Yamashita reported personal fees from KOTAI Biotechnologies, Inc. outside the submitted work; in addition, K. Yamashita had a patent to "follicular helper T cells specific for SARS-CoV-2 virus" pending and a patent to "novel medical technology using follicular T cells" pending. No other disclosures were reported.
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