Long-persisting SARS-CoV-2 spike-specific CD4+ T cells associated with mild disease and increased cytotoxicity post COVID-19
Issued Date
2025-12-01
Resource Type
eISSN
20411723
Scopus ID
2-s2.0-105017652596
Pubmed ID
41034205
Journal Title
Nature Communications
Volume
16
Issue
1
Rights Holder(s)
SCOPUS
Bibliographic Citation
Nature Communications Vol.16 No.1 (2025)
Suggested Citation
Liu G., Antoun E., Fries A., Yao X., Yin Z., Dong D., Wang W., Wing P.A.C., Dejnirattisa W., Supasa P., Liu C., Rostron T., Waugh C., Clark K., Sopp P., Fry J.W., Vendrell I., McKeating J.A., Mongkolsapaya J., Screaton G.R., Kessler B.M., Fisher R., Ogg G., Mentzer A.J., Knight J.C., Peng Y., Dong T. Long-persisting SARS-CoV-2 spike-specific CD4+ T cells associated with mild disease and increased cytotoxicity post COVID-19. Nature Communications Vol.16 No.1 (2025). doi:10.1038/s41467-025-63711-9 Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/112539
Title
Long-persisting SARS-CoV-2 spike-specific CD4+ T cells associated with mild disease and increased cytotoxicity post COVID-19
Corresponding Author(s)
Other Contributor(s)
Abstract
The recent COVID-19 pandemic left behind the lingering question as whether new variants of concern might cause further waves of infection. Thus, it is important to investigate the long-term protection gained via vaccination or exposure to the SARS-CoV-2 virus. Here we compare the evolution of memory T-cell responses following primary infection with subsequent antigen exposures. Single-cell TCR analysis of three dominant SARS-CoV-2 spike-specific CD4<sup>+</sup> T-cell responses identifies the dominant public TCRα clonotypes pairing with diverse TCRβ clonotypes that associated with mild disease at primary infection. These clonotypes are found at higher frequencies in pre-pandemic repertoires compared to other epitope-specific clonotypes. Longitudinal transcriptomics and TCR analysis, combined with functional evaluation, reveals that the clonotypes persisting 3–4 years post initial infection exhibit distinct functionality compared to those that were lost. Furthermore, spike-specific CD4<sup>+</sup> T cells at this time point show decreased Th1 signatures and enhanced GZMA-driven cytotoxic transcriptomic profiles that were independent of TCR clonotype and associated with viral suppression. In summary, we identify common public TCRs used by immunodominant spike-specific memory CD4<sup>+</sup> T-cells, associated with mild disease outcome, which likely play important protective roles to subsequent viral infection events.