tetano
Editor, Senior Moderator
Nat Commun
. 2025 Oct 1;16(1):8743.
doi: 10.1038/s41467-025-63711-9. Long-persisting SARS-CoV-2 spike-specific CD4[SUP]+[/SUP] T cells associated with mild disease and increased cytotoxicity post COVID-19
Guihai Liu[SUP] #[/SUP][SUP] 1 2 [/SUP], Elie Antoun[SUP] #[/SUP][SUP] 1 2 [/SUP], Anastasia Fries[SUP] 3 [/SUP], Xuan Yao[SUP] 1 2 [/SUP], Zixi Yin[SUP] 1 2 [/SUP], Danning Dong[SUP] 1 [/SUP], Wenbo Wang[SUP] 1 [/SUP], Peter A C Wing[SUP] 1 2 [/SUP], Wanwisa Dejnirattisa[SUP] 1 3 [/SUP], Piyada Supasa[SUP] 1 3 [/SUP], Chang Liu[SUP] 1 3 [/SUP], Timothy Rostron[SUP] 4 [/SUP], Craig Waugh[SUP] 5 [/SUP], Kevin Clark[SUP] 5 [/SUP], Paul Sopp[SUP] 5 [/SUP], Jeremy W Fry[SUP] 6 [/SUP], Iolanda Vendrell[SUP] 1 7 [/SUP], Jane A McKeating[SUP] 1 7 [/SUP], Juthathip Mongkolsapaya[SUP] 1 3 8 [/SUP], Gavin R Screaton[SUP] 1 3 [/SUP], Benedikt M Kessler[SUP] 1 7 [/SUP], Roman Fisher[SUP] 1 7 [/SUP], Graham Ogg[SUP] 1 9 [/SUP], Alexander J Mentzer[SUP] 1 3 [/SUP], Julian C Knight[SUP] 1 3 [/SUP], Yanchun Peng[SUP] 1 2 9 [/SUP], Tao Dong[SUP] 10 11 12 [/SUP]
Affiliations
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.
. 2025 Oct 1;16(1):8743.
doi: 10.1038/s41467-025-63711-9. Long-persisting SARS-CoV-2 spike-specific CD4[SUP]+[/SUP] T cells associated with mild disease and increased cytotoxicity post COVID-19
Guihai Liu[SUP] #[/SUP][SUP] 1 2 [/SUP], Elie Antoun[SUP] #[/SUP][SUP] 1 2 [/SUP], Anastasia Fries[SUP] 3 [/SUP], Xuan Yao[SUP] 1 2 [/SUP], Zixi Yin[SUP] 1 2 [/SUP], Danning Dong[SUP] 1 [/SUP], Wenbo Wang[SUP] 1 [/SUP], Peter A C Wing[SUP] 1 2 [/SUP], Wanwisa Dejnirattisa[SUP] 1 3 [/SUP], Piyada Supasa[SUP] 1 3 [/SUP], Chang Liu[SUP] 1 3 [/SUP], Timothy Rostron[SUP] 4 [/SUP], Craig Waugh[SUP] 5 [/SUP], Kevin Clark[SUP] 5 [/SUP], Paul Sopp[SUP] 5 [/SUP], Jeremy W Fry[SUP] 6 [/SUP], Iolanda Vendrell[SUP] 1 7 [/SUP], Jane A McKeating[SUP] 1 7 [/SUP], Juthathip Mongkolsapaya[SUP] 1 3 8 [/SUP], Gavin R Screaton[SUP] 1 3 [/SUP], Benedikt M Kessler[SUP] 1 7 [/SUP], Roman Fisher[SUP] 1 7 [/SUP], Graham Ogg[SUP] 1 9 [/SUP], Alexander J Mentzer[SUP] 1 3 [/SUP], Julian C Knight[SUP] 1 3 [/SUP], Yanchun Peng[SUP] 1 2 9 [/SUP], Tao Dong[SUP] 10 11 12 [/SUP]
Affiliations
- PMID: 41034205
- DOI: 10.1038/s41467-025-63711-9
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.