tetano
Editor, Senior Moderator
Microbiol Spectr
. 2023 Jul 10;e0214323.
doi: 10.1128/spectrum.02143-23. Online ahead of print. Breadth and Durability of SARS-CoV-2-Specific T Cell Responses following Long-Term Recovery from COVID-19
Thi Thu Thao Dang[SUP] 1 2 [/SUP], Alitzel Anzurez[SUP] 1 2 [/SUP], Kaori Nakayama-Hosoya[SUP] 1 [/SUP], Shoji Miki[SUP] 1 [/SUP], Kazuo Yamashita[SUP] 3 [/SUP], Mark de Souza[SUP] 1 [/SUP], Tetsuro Matano[SUP] 1 2 4 [/SUP], Ai Kawana-Tachikawa[SUP] 1 2 4 [/SUP]
Affiliations
T cell immunity is crucial for long-term immunological memory, but the profile of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific memory T cells in individuals who recovered from COVID-19 (COVID-19-convalescent individuals) is not sufficiently assessed. In this study, the breadth and magnitude of SARS-CoV-2-specific T cell responses were determined in COVID-19-convalescent individuals in Japan. Memory T cells against SARS-CoV-2 were detected in all convalescent individuals, and those with more severe disease exhibited a broader T cell response relative to cases with mild symptoms. Comprehensive screening of T cell responses at the peptide level was conducted for spike (S) and nucleocapsid (N) proteins, and regions frequently targeted by T cells were identified. Multiple regions in S and N proteins were targeted by memory T cells, with median numbers of target regions of 13 and 4, respectively. A maximum of 47 regions were recognized by memory T cells for an individual. These data indicate that SARS-CoV-2-convalescent individuals maintain a substantial breadth of memory T cells for at least several months following infection. Broader SARS-CoV-2-specific CD4[SUP]+[/SUP] T cell responses, relative to CD8[SUP]+[/SUP] T cell responses, were observed for the S but not the N protein, suggesting that antigen presentation is different between viral proteins. The binding affinity of predicted CD8[SUP]+[/SUP] T cell epitopes to HLA class I molecules in these regions was preserved for the Delta variant and at 94 to 96% for SARS-CoV-2 Omicron subvariants, suggesting that the amino acid changes in these variants do not have a major impact on antigen presentation to SARS-CoV-2-specific CD8[SUP]+[/SUP] T cells. IMPORTANCE RNA viruses, including SARS-CoV-2, evade host immune responses through mutations. As broader T cell responses against multiple viral proteins could minimize the impact of each single amino acid mutation, the breadth of memory T cells would be one essential parameter for effective protection. In this study, breadth of memory T cells to S and N proteins was assessed in COVID-19-convalescent individuals. While broad T cell responses were induced against both proteins, the ratio of N to S proteins for breadth of T cell responses was significantly higher in milder cases. The breadth of CD4[SUP]+[/SUP] and CD8[SUP]+[/SUP] T cell responses was also significantly different between S and N proteins, suggesting different contributions of N and S protein-specific T cells for COVID-19 control. Most CD8[SUP]+[/SUP] T cell epitopes in the immunodominant regions maintained their HLA binding to SARS-CoV-2 Omicron subvariants. Our study provides insights into understanding the protective efficacy of SARS-CoV-2-specific memory T cells against reinfection.
Keywords: COVID-19; SARS-CoV-2; T cell immunity; variants.
. 2023 Jul 10;e0214323.
doi: 10.1128/spectrum.02143-23. Online ahead of print. Breadth and Durability of SARS-CoV-2-Specific T Cell Responses following Long-Term Recovery from COVID-19
Thi Thu Thao Dang[SUP] 1 2 [/SUP], Alitzel Anzurez[SUP] 1 2 [/SUP], Kaori Nakayama-Hosoya[SUP] 1 [/SUP], Shoji Miki[SUP] 1 [/SUP], Kazuo Yamashita[SUP] 3 [/SUP], Mark de Souza[SUP] 1 [/SUP], Tetsuro Matano[SUP] 1 2 4 [/SUP], Ai Kawana-Tachikawa[SUP] 1 2 4 [/SUP]
Affiliations
- PMID: 37428088
- DOI: 10.1128/spectrum.02143-23
T cell immunity is crucial for long-term immunological memory, but the profile of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific memory T cells in individuals who recovered from COVID-19 (COVID-19-convalescent individuals) is not sufficiently assessed. In this study, the breadth and magnitude of SARS-CoV-2-specific T cell responses were determined in COVID-19-convalescent individuals in Japan. Memory T cells against SARS-CoV-2 were detected in all convalescent individuals, and those with more severe disease exhibited a broader T cell response relative to cases with mild symptoms. Comprehensive screening of T cell responses at the peptide level was conducted for spike (S) and nucleocapsid (N) proteins, and regions frequently targeted by T cells were identified. Multiple regions in S and N proteins were targeted by memory T cells, with median numbers of target regions of 13 and 4, respectively. A maximum of 47 regions were recognized by memory T cells for an individual. These data indicate that SARS-CoV-2-convalescent individuals maintain a substantial breadth of memory T cells for at least several months following infection. Broader SARS-CoV-2-specific CD4[SUP]+[/SUP] T cell responses, relative to CD8[SUP]+[/SUP] T cell responses, were observed for the S but not the N protein, suggesting that antigen presentation is different between viral proteins. The binding affinity of predicted CD8[SUP]+[/SUP] T cell epitopes to HLA class I molecules in these regions was preserved for the Delta variant and at 94 to 96% for SARS-CoV-2 Omicron subvariants, suggesting that the amino acid changes in these variants do not have a major impact on antigen presentation to SARS-CoV-2-specific CD8[SUP]+[/SUP] T cells. IMPORTANCE RNA viruses, including SARS-CoV-2, evade host immune responses through mutations. As broader T cell responses against multiple viral proteins could minimize the impact of each single amino acid mutation, the breadth of memory T cells would be one essential parameter for effective protection. In this study, breadth of memory T cells to S and N proteins was assessed in COVID-19-convalescent individuals. While broad T cell responses were induced against both proteins, the ratio of N to S proteins for breadth of T cell responses was significantly higher in milder cases. The breadth of CD4[SUP]+[/SUP] and CD8[SUP]+[/SUP] T cell responses was also significantly different between S and N proteins, suggesting different contributions of N and S protein-specific T cells for COVID-19 control. Most CD8[SUP]+[/SUP] T cell epitopes in the immunodominant regions maintained their HLA binding to SARS-CoV-2 Omicron subvariants. Our study provides insights into understanding the protective efficacy of SARS-CoV-2-specific memory T cells against reinfection.
Keywords: COVID-19; SARS-CoV-2; T cell immunity; variants.