Identification of conserved SARS-CoV-2 spike epitopes that expand public cTfh clonotypes in mild COVID-19 patients
Open Access
- 14 October 2021
- journal article
- research article
- Published by Rockefeller University Press in The Journal of Experimental Medicine
- Vol. 218 (12)
- https://doi.org/10.1084/jem.20211327
Abstract
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.Keywords
Funding Information
- Japan Agency for Medical Research and Development (20fk0108265, 20nk0101602, 20fk0108454, 21nf0101623, 21gm0910010, 21ak0101070, 20fk0108075, 20fk0108104, 21fk0108608, 21fk0108534, 20fk0108542, 20fk0108403)
- Japan Society for the Promotion of Science (JP18H05279, JP20H00505)
- Kansai Economic Federation
- Mitsubishi Foundation
- AnGes
- Daicel
- FunPep
This publication has 58 references indexed in Scilit:
- Phenotype and functions of memory Tfh cells in human bloodTrends in Immunology, 2014
- Human Circulating PD-1+CXCR3−CXCR5+ Memory Tfh Cells Are Highly Functional and Correlate with Broadly Neutralizing HIV Antibody ResponsesImmunity, 2013
- Transcriptional regulation of follicular T‐helper (Tfh) cellsImmunological Reviews, 2013
- Transport of misfolded endoplasmic reticulum proteins to the cell surface by MHC class II moleculesInternational Immunology, 2013
- Towards automated crystallographic structure refinement with phenix.refineActa crystallographica. Section D, Structural biology, 2012
- Features and development of CootActa crystallographica. Section D, Structural biology, 2010
- XDSActa crystallographica. Section D, Structural biology, 2010
- Molecular replacement withMOLREPActa crystallographica. Section D, Structural biology, 2009
- Scaling and assessment of data qualityActa crystallographica. Section D, Structural biology, 2005
- REFMAC5 dictionary: organization of prior chemical knowledge and guidelines for its useActa crystallographica. Section D, Structural biology, 2004