tetano
Editor, Senior Moderator
Signal Transduct Target Ther
. 2024 Jun 12;9(1):160.
doi: 10.1038/s41392-024-01876-3. Nonconserved epitopes dominate reverse preexisting T cell immunity in COVID-19 convalescents
Xin Wang[SUP] #[/SUP][SUP] 1 2 [/SUP], Jie Zhang[SUP] #[/SUP][SUP] 3 4 5 [/SUP], Maoshun Liu[SUP] 2 6 [/SUP], Yuanyuan Guo[SUP] 1 2 [/SUP], Peipei Guo[SUP] 1 2 [/SUP], Xiaonan Yang[SUP] 1 2 [/SUP], Bingli Shang[SUP] 2 6 [/SUP], Min Li[SUP] 2 [/SUP], Jinmin Tian[SUP] 2 7 [/SUP], Ting Zhang[SUP] 2 8 [/SUP], Xi Wang[SUP] 3 4 5 [/SUP], Ronghua Jin[SUP] 3 4 5 [/SUP], Jikun Zhou[SUP] 9 [/SUP], George F Gao[SUP] 10 11 12 [/SUP], Jun Liu[SUP] 13 14 [/SUP]
Affiliations
The herd immunity against SARS-CoV-2 is continuously consolidated across the world during the ongoing pandemic. However, the potential function of the nonconserved epitopes in the reverse preexisting cross-reactivity induced by SARS-CoV-2 to other human coronaviruses is not well explored. In our research, we assessed T cell responses to both conserved and nonconserved peptides shared by SARS-CoV-2 and SARS-CoV, identifying cross-reactive CD8[SUP]+[/SUP] T cell epitopes using enzyme-linked immunospot and intracellular cytokine staining assays. Then, in vitro refolding and circular dichroism were performed to evaluate the thermal stability of the HLA/peptide complexes. Lastly, single-cell T cell receptor reservoir was analyzed based on tetramer staining. Here, we discovered that cross-reactive T cells targeting SARS-CoV were present in individuals who had recovered from COVID-19, and identified SARS-CoV-2 CD8[SUP]+[/SUP] T cell epitopes spanning the major structural antigens. T cell responses induced by the nonconserved peptides between SARS-CoV-2 and SARS-CoV were higher and played a dominant role in the cross-reactivity in COVID-19 convalescents. Cross-T cell reactivity was also observed within the identified series of CD8[SUP]+[/SUP] T cell epitopes. For representative immunodominant peptide pairs, although the HLA binding capacities for peptides from SARS-CoV-2 and SARS-CoV were similar, the TCR repertoires recognizing these peptides were distinct. Our results could provide beneficial information for the development of peptide-based universal vaccines against coronaviruses.
. 2024 Jun 12;9(1):160.
doi: 10.1038/s41392-024-01876-3. Nonconserved epitopes dominate reverse preexisting T cell immunity in COVID-19 convalescents
Xin Wang[SUP] #[/SUP][SUP] 1 2 [/SUP], Jie Zhang[SUP] #[/SUP][SUP] 3 4 5 [/SUP], Maoshun Liu[SUP] 2 6 [/SUP], Yuanyuan Guo[SUP] 1 2 [/SUP], Peipei Guo[SUP] 1 2 [/SUP], Xiaonan Yang[SUP] 1 2 [/SUP], Bingli Shang[SUP] 2 6 [/SUP], Min Li[SUP] 2 [/SUP], Jinmin Tian[SUP] 2 7 [/SUP], Ting Zhang[SUP] 2 8 [/SUP], Xi Wang[SUP] 3 4 5 [/SUP], Ronghua Jin[SUP] 3 4 5 [/SUP], Jikun Zhou[SUP] 9 [/SUP], George F Gao[SUP] 10 11 12 [/SUP], Jun Liu[SUP] 13 14 [/SUP]
Affiliations
- PMID: 38866784
- DOI: 10.1038/s41392-024-01876-3
The herd immunity against SARS-CoV-2 is continuously consolidated across the world during the ongoing pandemic. However, the potential function of the nonconserved epitopes in the reverse preexisting cross-reactivity induced by SARS-CoV-2 to other human coronaviruses is not well explored. In our research, we assessed T cell responses to both conserved and nonconserved peptides shared by SARS-CoV-2 and SARS-CoV, identifying cross-reactive CD8[SUP]+[/SUP] T cell epitopes using enzyme-linked immunospot and intracellular cytokine staining assays. Then, in vitro refolding and circular dichroism were performed to evaluate the thermal stability of the HLA/peptide complexes. Lastly, single-cell T cell receptor reservoir was analyzed based on tetramer staining. Here, we discovered that cross-reactive T cells targeting SARS-CoV were present in individuals who had recovered from COVID-19, and identified SARS-CoV-2 CD8[SUP]+[/SUP] T cell epitopes spanning the major structural antigens. T cell responses induced by the nonconserved peptides between SARS-CoV-2 and SARS-CoV were higher and played a dominant role in the cross-reactivity in COVID-19 convalescents. Cross-T cell reactivity was also observed within the identified series of CD8[SUP]+[/SUP] T cell epitopes. For representative immunodominant peptide pairs, although the HLA binding capacities for peptides from SARS-CoV-2 and SARS-CoV were similar, the TCR repertoires recognizing these peptides were distinct. Our results could provide beneficial information for the development of peptide-based universal vaccines against coronaviruses.