tetano
Editor, Senior Moderator
Heliyon
. 2023 Sep 20;9(9):e20192.
doi: 10.1016/j.heliyon.2023.e20192. eCollection 2023 Sep. SARS-CoV-2 spike protein-derived immunogenic peptides that are promiscuously presented by several HLA-class II molecules and their potential for inducing acquired immunity
Yuki Yajima[SUP] 1 2 [/SUP], Akemi Kosaka[SUP] 2 [/SUP], Takayuki Ohkuri[SUP] 2 [/SUP], Yoshihiko Hirohashi[SUP] 3 [/SUP], Dongliang Li[SUP] 4 [/SUP], Takeshi Nagasaki[SUP] 4 [/SUP], Toshihiro Nagato[SUP] 2 [/SUP], Toshihiko Torigoe[SUP] 3 [/SUP], Hiroya Kobayashi[SUP] 2 [/SUP]
Affiliations
The current coronavirus disease 2019 (COVID-19) pandemic that is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has a significant threat to public health. Although vaccines based on the mRNA of the SARS-CoV-2 spike protein have been developed to induce both cellular and humoral immunity against SARS-CoV-2, there have been some concerns raised about their high cost, particularly in developing countries. In the present study, we aim to identify an immunogenic peptide in the SARS-CoV-2 spike protein to activate cellular immunity, particularly CD4[SUP]+[/SUP] helper T lymphocytes (Th cells), which are a commander of immune system. SARS-CoV-2 spike protein-derived peptides Spike[SUB]448-477[/SUB] and Spike[SUB]489-513(N501Y)[/SUB]-specific CD4[SUP]+[/SUP] Th cell lines were generated by repetitive stimulation of healthy donor-derived CD4[SUP]+[/SUP]T-cells with each peptide. Their HLA-restrictions were addressed by using blocking antibodies against HLA and HLA-transfected L-cells. The epitopes of Spike[SUB]448-477[/SUB]-specific CD4[SUP]+[/SUP] Th cell lines were defined using a series of 7-14-mer overlapping truncated peptides and alanine-substituted epitope peptides. To address responsiveness of these CD4[SUP]+[/SUP] Th cell lines to several SARS-CoV-2 variants, we stimulated the CD4[SUP]+[/SUP] Th cell lines with mutated peptides. We addressed whether these identified peptides were useful for monitoring T-cell-based immune responses in vaccinated donors using the IFN-γ ELISpot assay. The Spike[SUB]448-477[/SUB] peptide was found to be a promiscuous peptide presented by HLA- DRB1*08:02, DR53, and DPB1*02:02. Although HLA-DPB1*02:02-restricted CD4[SUP]+[/SUP] Th cells did not response to some peptides with the L452R and L452Q mutations, the other CD4[SUP]+[/SUP] Th cells were not affected by any mutant peptides. We developed two tetramers to detect HLA-DRB1*08:02/Spike[SUB]449-463[/SUB]- and Spike[SUB]449-463[/SUB](L452R/Y453F)-recognizing CD4[SUP]+[/SUP] Th cells. Spike[SUB]489-513(N501Y)[/SUB] peptide was also a promiscuously presented to HLA-DRB1*09:01 and DRB1*15:02. The T-cell responses specific to both peptides Spike[SUB]448-477[/SUB] and Spike[SUB]489-513[/SUB] were detected in PBMCs after vaccinations. In addition, we observed that the Spike[SUB]448-477[/SUB] peptide activated both CD8[SUP]+[/SUP] T-cells and CD4[SUP]+[/SUP] Th cells in individuals receiving mRNA vaccines. SARS-CoV-2 spike protein-derived peptides, Spike[SUB]448-477[/SUB] and Spike[SUB]489-513[/SUB], include several epitopes that are presented by multiple HLA-class II alleles to activate CD4[SUP]+[/SUP] Th cells, which are considered useful for monitoring the establishment of acquired immunity after vaccination.
Keywords: Cellular immunity; Helper T lymphocytes; SARS-CoV-2; T-cell monitoring.
. 2023 Sep 20;9(9):e20192.
doi: 10.1016/j.heliyon.2023.e20192. eCollection 2023 Sep. SARS-CoV-2 spike protein-derived immunogenic peptides that are promiscuously presented by several HLA-class II molecules and their potential for inducing acquired immunity
Yuki Yajima[SUP] 1 2 [/SUP], Akemi Kosaka[SUP] 2 [/SUP], Takayuki Ohkuri[SUP] 2 [/SUP], Yoshihiko Hirohashi[SUP] 3 [/SUP], Dongliang Li[SUP] 4 [/SUP], Takeshi Nagasaki[SUP] 4 [/SUP], Toshihiro Nagato[SUP] 2 [/SUP], Toshihiko Torigoe[SUP] 3 [/SUP], Hiroya Kobayashi[SUP] 2 [/SUP]
Affiliations
- PMID: 37809871
- PMCID: PMC10559948
- DOI: 10.1016/j.heliyon.2023.e20192
The current coronavirus disease 2019 (COVID-19) pandemic that is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has a significant threat to public health. Although vaccines based on the mRNA of the SARS-CoV-2 spike protein have been developed to induce both cellular and humoral immunity against SARS-CoV-2, there have been some concerns raised about their high cost, particularly in developing countries. In the present study, we aim to identify an immunogenic peptide in the SARS-CoV-2 spike protein to activate cellular immunity, particularly CD4[SUP]+[/SUP] helper T lymphocytes (Th cells), which are a commander of immune system. SARS-CoV-2 spike protein-derived peptides Spike[SUB]448-477[/SUB] and Spike[SUB]489-513(N501Y)[/SUB]-specific CD4[SUP]+[/SUP] Th cell lines were generated by repetitive stimulation of healthy donor-derived CD4[SUP]+[/SUP]T-cells with each peptide. Their HLA-restrictions were addressed by using blocking antibodies against HLA and HLA-transfected L-cells. The epitopes of Spike[SUB]448-477[/SUB]-specific CD4[SUP]+[/SUP] Th cell lines were defined using a series of 7-14-mer overlapping truncated peptides and alanine-substituted epitope peptides. To address responsiveness of these CD4[SUP]+[/SUP] Th cell lines to several SARS-CoV-2 variants, we stimulated the CD4[SUP]+[/SUP] Th cell lines with mutated peptides. We addressed whether these identified peptides were useful for monitoring T-cell-based immune responses in vaccinated donors using the IFN-γ ELISpot assay. The Spike[SUB]448-477[/SUB] peptide was found to be a promiscuous peptide presented by HLA- DRB1*08:02, DR53, and DPB1*02:02. Although HLA-DPB1*02:02-restricted CD4[SUP]+[/SUP] Th cells did not response to some peptides with the L452R and L452Q mutations, the other CD4[SUP]+[/SUP] Th cells were not affected by any mutant peptides. We developed two tetramers to detect HLA-DRB1*08:02/Spike[SUB]449-463[/SUB]- and Spike[SUB]449-463[/SUB](L452R/Y453F)-recognizing CD4[SUP]+[/SUP] Th cells. Spike[SUB]489-513(N501Y)[/SUB] peptide was also a promiscuously presented to HLA-DRB1*09:01 and DRB1*15:02. The T-cell responses specific to both peptides Spike[SUB]448-477[/SUB] and Spike[SUB]489-513[/SUB] were detected in PBMCs after vaccinations. In addition, we observed that the Spike[SUB]448-477[/SUB] peptide activated both CD8[SUP]+[/SUP] T-cells and CD4[SUP]+[/SUP] Th cells in individuals receiving mRNA vaccines. SARS-CoV-2 spike protein-derived peptides, Spike[SUB]448-477[/SUB] and Spike[SUB]489-513[/SUB], include several epitopes that are presented by multiple HLA-class II alleles to activate CD4[SUP]+[/SUP] Th cells, which are considered useful for monitoring the establishment of acquired immunity after vaccination.
Keywords: Cellular immunity; Helper T lymphocytes; SARS-CoV-2; T-cell monitoring.