tetano
Editor, Senior Moderator
Elife
. 2024 May 8:12:RP89999.
doi: 10.7554/eLife.89999. Early acquisition of S-specific Tfh clonotypes after SARS-CoV-2 vaccination is associated with the longevity of anti-S antibodies
Xiuyuan Lu[SUP] #[/SUP][SUP] 1 [/SUP], Hiroki Hayashi[SUP] #[/SUP][SUP] 2 [/SUP], Eri Ishikawa[SUP] #[/SUP][SUP] 1 3 [/SUP], Yukiko Takeuchi[SUP] 1 [/SUP], Julian Vincent Tabora Dychiao[SUP] 1 [/SUP], Hironori Nakagami[SUP] 2 [/SUP], Sho Yamasaki[SUP] 1 3 4 [/SUP]
Affiliations
SARS-CoV-2 vaccines have been used worldwide to combat COVID-19 pandemic. To elucidate the factors that determine the longevity of spike (S)-specific antibodies, we traced the characteristics of S-specific T cell clonotypes together with their epitopes and anti-S antibody titers before and after BNT162b2 vaccination over time. T cell receptor (TCR) αβ sequences and mRNA expression of the S-responded T cells were investigated using single-cell TCR- and RNA-sequencing. Highly expanded 199 TCR clonotypes upon stimulation with S peptide pools were reconstituted into a reporter T cell line for the determination of epitopes and restricting HLAs. Among them, we could determine 78 S epitopes, most of which were conserved in variants of concern (VOCs). After the 2nd vaccination, T cell clonotypes highly responsive to recall S stimulation were polarized to follicular helper T (Tfh)-like cells in donors exhibiting sustained anti-S antibody titers (designated as 'sustainers'), but not in 'decliners'. Even before vaccination, S-reactive CD4[SUP]+[/SUP] T cell clonotypes did exist, most of which cross-reacted with environmental or symbiotic microbes. However, these clonotypes contracted after vaccination. Conversely, S-reactive clonotypes dominated after vaccination were undetectable in pre-vaccinated T cell pool, suggesting that highly responding S-reactive T cells were established by vaccination from rare clonotypes. These results suggest that de novo acquisition of memory Tfh-like cells upon vaccination may contribute to the longevity of anti-S antibody titers.
Keywords: SARS-CoV-2; T cell response; Tfh cells; antibody longevity; clonotypic tracing; human; immunology; inflammation; vaccine.
. 2024 May 8:12:RP89999.
doi: 10.7554/eLife.89999. Early acquisition of S-specific Tfh clonotypes after SARS-CoV-2 vaccination is associated with the longevity of anti-S antibodies
Xiuyuan Lu[SUP] #[/SUP][SUP] 1 [/SUP], Hiroki Hayashi[SUP] #[/SUP][SUP] 2 [/SUP], Eri Ishikawa[SUP] #[/SUP][SUP] 1 3 [/SUP], Yukiko Takeuchi[SUP] 1 [/SUP], Julian Vincent Tabora Dychiao[SUP] 1 [/SUP], Hironori Nakagami[SUP] 2 [/SUP], Sho Yamasaki[SUP] 1 3 4 [/SUP]
Affiliations
- PMID: 38716629
- PMCID: PMC11078543
- DOI: 10.7554/eLife.89999
SARS-CoV-2 vaccines have been used worldwide to combat COVID-19 pandemic. To elucidate the factors that determine the longevity of spike (S)-specific antibodies, we traced the characteristics of S-specific T cell clonotypes together with their epitopes and anti-S antibody titers before and after BNT162b2 vaccination over time. T cell receptor (TCR) αβ sequences and mRNA expression of the S-responded T cells were investigated using single-cell TCR- and RNA-sequencing. Highly expanded 199 TCR clonotypes upon stimulation with S peptide pools were reconstituted into a reporter T cell line for the determination of epitopes and restricting HLAs. Among them, we could determine 78 S epitopes, most of which were conserved in variants of concern (VOCs). After the 2nd vaccination, T cell clonotypes highly responsive to recall S stimulation were polarized to follicular helper T (Tfh)-like cells in donors exhibiting sustained anti-S antibody titers (designated as 'sustainers'), but not in 'decliners'. Even before vaccination, S-reactive CD4[SUP]+[/SUP] T cell clonotypes did exist, most of which cross-reacted with environmental or symbiotic microbes. However, these clonotypes contracted after vaccination. Conversely, S-reactive clonotypes dominated after vaccination were undetectable in pre-vaccinated T cell pool, suggesting that highly responding S-reactive T cells were established by vaccination from rare clonotypes. These results suggest that de novo acquisition of memory Tfh-like cells upon vaccination may contribute to the longevity of anti-S antibody titers.
Keywords: SARS-CoV-2; T cell response; Tfh cells; antibody longevity; clonotypic tracing; human; immunology; inflammation; vaccine.