tetano
Editor, Senior Moderator
iScience
. 2026 Apr 24;29(6):115880.
doi: 10.1016/j.isci.2026.115880. eCollection 2026 Jun 19.
Distinct CD8[SUP]+[/SUP] T cell types associated with COVID-19 severity in unvaccinated HLA-A2[SUP]+[/SUP] patients
Kazuya Masuda[SUP] 1 2 [/SUP], Sho Iketani[SUP] 1 2 3 [/SUP], Lihong Liu[SUP] 1 2 [/SUP], Jing Huang[SUP] 1 2 [/SUP], Yujie Qiao[SUP] 1 2 [/SUP], Jayesh Shah[SUP] 2 [/SUP], Meredith L McNairy[SUP] 2 [/SUP], Christine Groso[SUP] 1 2 [/SUP], Christopher L Ricupero[SUP] 4 [/SUP], Lucas F Loffredo[SUP] 3 [/SUP], Qian Wang[SUP] 1 2 [/SUP], Lawrence Purpura[SUP] 2 [/SUP], Jordana Grazziela Alves Coelho-Dos-Reis[SUP] 5 [/SUP], Zizhang Sheng[SUP] 1 2 [/SUP], Michael T Yin[SUP] 1 2 [/SUP], Moriya Tsuji[SUP] 1 2 [/SUP]
Affiliations
Despite emerging studies about coronavirus disease 2019 (COVID-19)-associated adaptive immune responses, CD8[SUP]+[/SUP] T cell immunity in the context of HLA restriction, particularly in unvaccinated patients, remains largely uncharacterized. Here, we show that in HLA-A2-positive patients with COVID-19, cell-mediated immune responses are crucial in determining disease severity, irrespective of humoral immune responses. We observe robust cell-mediated immune responses against our selected, highly conserved 9-mer severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) epitopes in mild patients but poor responsiveness in severe patients. Single-cell analyses of HLA-A2-restricted CD8[SUP]+[/SUP] T cells against those epitopes reveal distinct cellular profiles between mild and severe COVID-19. In mild COVID-19, effector KLRB1 [SUP]+[/SUP] innate-like cells, IFNG [SUP]hi[/SUP] ID3 [SUP]hi[/SUP] memory cells, and IL7R [SUP]+[/SUP] proliferative stem cell-like memory cells are preferentially detected. By contrast, severe cases are featured by dysfunctional T cell types, particularly early terminated and terminally differentiated subtypes. Thus, our findings suggest that contrasting HLA-A2-restricted SARS-CoV-2 epitope-specific CD8[SUP]+[/SUP] T cell profiles reflect the magnitude of cellular immune responses, potentially affecting disease severity.
Keywords: Bioinformatics; Immunology.
. 2026 Apr 24;29(6):115880.
doi: 10.1016/j.isci.2026.115880. eCollection 2026 Jun 19.
Distinct CD8[SUP]+[/SUP] T cell types associated with COVID-19 severity in unvaccinated HLA-A2[SUP]+[/SUP] patients
Kazuya Masuda[SUP] 1 2 [/SUP], Sho Iketani[SUP] 1 2 3 [/SUP], Lihong Liu[SUP] 1 2 [/SUP], Jing Huang[SUP] 1 2 [/SUP], Yujie Qiao[SUP] 1 2 [/SUP], Jayesh Shah[SUP] 2 [/SUP], Meredith L McNairy[SUP] 2 [/SUP], Christine Groso[SUP] 1 2 [/SUP], Christopher L Ricupero[SUP] 4 [/SUP], Lucas F Loffredo[SUP] 3 [/SUP], Qian Wang[SUP] 1 2 [/SUP], Lawrence Purpura[SUP] 2 [/SUP], Jordana Grazziela Alves Coelho-Dos-Reis[SUP] 5 [/SUP], Zizhang Sheng[SUP] 1 2 [/SUP], Michael T Yin[SUP] 1 2 [/SUP], Moriya Tsuji[SUP] 1 2 [/SUP]
Affiliations
- PMID: 42181242
- PMCID: PMC13195792
- DOI: 10.1016/j.isci.2026.115880
Despite emerging studies about coronavirus disease 2019 (COVID-19)-associated adaptive immune responses, CD8[SUP]+[/SUP] T cell immunity in the context of HLA restriction, particularly in unvaccinated patients, remains largely uncharacterized. Here, we show that in HLA-A2-positive patients with COVID-19, cell-mediated immune responses are crucial in determining disease severity, irrespective of humoral immune responses. We observe robust cell-mediated immune responses against our selected, highly conserved 9-mer severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) epitopes in mild patients but poor responsiveness in severe patients. Single-cell analyses of HLA-A2-restricted CD8[SUP]+[/SUP] T cells against those epitopes reveal distinct cellular profiles between mild and severe COVID-19. In mild COVID-19, effector KLRB1 [SUP]+[/SUP] innate-like cells, IFNG [SUP]hi[/SUP] ID3 [SUP]hi[/SUP] memory cells, and IL7R [SUP]+[/SUP] proliferative stem cell-like memory cells are preferentially detected. By contrast, severe cases are featured by dysfunctional T cell types, particularly early terminated and terminally differentiated subtypes. Thus, our findings suggest that contrasting HLA-A2-restricted SARS-CoV-2 epitope-specific CD8[SUP]+[/SUP] T cell profiles reflect the magnitude of cellular immune responses, potentially affecting disease severity.
Keywords: Bioinformatics; Immunology.