tetano
Editor, Senior Moderator
Eur J Immunol
. 2025 Apr;55(4):e202451497.
doi: 10.1002/eji.202451497. Distinct HLA Haplotypes Are Associated With an Altered Strength of SARS-CoV-2-Specific T-Cell Responses and Unfavorable Disease Courses
C Dörnte[SUP] 1 2 [/SUP], A Datsi[SUP] 3 [/SUP], V Traska[SUP] 1 [/SUP], J Kostyra[SUP] 1 [/SUP], M Wagner[SUP] 1 [/SUP], O Brauns[SUP] 1 [/SUP], C Lamsfuß[SUP] 1 [/SUP], H Winkels[SUP] 2 4 [/SUP], V Balz[SUP] 3 [/SUP], J Enczmann[SUP] 3 [/SUP], O Adams[SUP] 5 [/SUP], L Mueller[SUP] 5 [/SUP], H Baurmann[SUP] 1 [/SUP], B Eiz-Vesper[SUP] 6 [/SUP], A Bonifacius[SUP] 6 [/SUP], R V Sorg[SUP] 3 [/SUP], C Dose[SUP] 1 [/SUP], J Schmitz[SUP] 1 [/SUP], A Richter[SUP] 1 [/SUP], J Fischer[SUP] 3 [/SUP], M Schuster[SUP] 1 [/SUP]
Affiliations
Infection with SARS-CoV-2 results in mild to severe COVID-19 disease courses. Several studies showed the association of impaired T-cell responses and certain HLA haplotypes with disease severity. However, it remained unclear if T-cell activation was compromised due to a general reduction of presented epitopes or other intrinsic factors within APCs or T cells. Furthermore, a potential reduction of presented epitopes would suggest if an upcoming SARS-CoV-2 variant could escape T-cell immunity. Hence, knowledge about the T-cell epitope landscape of SARS-CoV-2 would allow to better understand mechanisms leading to severe disease and to estimate the potential stability of the T-cell response in light of virus evolution, which might provide insights for future vaccine designs. Hence, in the present study, the T-cell epitope landscape of SARS-CoV-2 was determined via in vitro T-cell stimulation plus in silico prediction. HLAs associated with mild and severe disease courses showed almost the same potential in epitope presentation, suggesting intrinsic factors of APCs or T cells as contributors to the more severe disease courses. As T-cell epitopes did also not originate from regions of SARS-CoV-2 having shown high mutation rates in the past, a relatively stable T-cell response can be expected regarding new SARS-CoV-2 strains in the future. Analysis of the T-cell epitope landscape of SARS-CoV-2 suggests T-cell intrinsic factors as likely modulators of disease severity and that the capacity of MHC-peptide presentation remains stable among circulating SARS-CoV-2 viral strains.
Keywords: APC; HLA haplotypes; NetMHCpan; SARS‐CoV‐2; T‐cell immunity.
. 2025 Apr;55(4):e202451497.
doi: 10.1002/eji.202451497. Distinct HLA Haplotypes Are Associated With an Altered Strength of SARS-CoV-2-Specific T-Cell Responses and Unfavorable Disease Courses
C Dörnte[SUP] 1 2 [/SUP], A Datsi[SUP] 3 [/SUP], V Traska[SUP] 1 [/SUP], J Kostyra[SUP] 1 [/SUP], M Wagner[SUP] 1 [/SUP], O Brauns[SUP] 1 [/SUP], C Lamsfuß[SUP] 1 [/SUP], H Winkels[SUP] 2 4 [/SUP], V Balz[SUP] 3 [/SUP], J Enczmann[SUP] 3 [/SUP], O Adams[SUP] 5 [/SUP], L Mueller[SUP] 5 [/SUP], H Baurmann[SUP] 1 [/SUP], B Eiz-Vesper[SUP] 6 [/SUP], A Bonifacius[SUP] 6 [/SUP], R V Sorg[SUP] 3 [/SUP], C Dose[SUP] 1 [/SUP], J Schmitz[SUP] 1 [/SUP], A Richter[SUP] 1 [/SUP], J Fischer[SUP] 3 [/SUP], M Schuster[SUP] 1 [/SUP]
Affiliations
- PMID: 40259456
- PMCID: PMC12012228
- DOI: 10.1002/eji.202451497
Infection with SARS-CoV-2 results in mild to severe COVID-19 disease courses. Several studies showed the association of impaired T-cell responses and certain HLA haplotypes with disease severity. However, it remained unclear if T-cell activation was compromised due to a general reduction of presented epitopes or other intrinsic factors within APCs or T cells. Furthermore, a potential reduction of presented epitopes would suggest if an upcoming SARS-CoV-2 variant could escape T-cell immunity. Hence, knowledge about the T-cell epitope landscape of SARS-CoV-2 would allow to better understand mechanisms leading to severe disease and to estimate the potential stability of the T-cell response in light of virus evolution, which might provide insights for future vaccine designs. Hence, in the present study, the T-cell epitope landscape of SARS-CoV-2 was determined via in vitro T-cell stimulation plus in silico prediction. HLAs associated with mild and severe disease courses showed almost the same potential in epitope presentation, suggesting intrinsic factors of APCs or T cells as contributors to the more severe disease courses. As T-cell epitopes did also not originate from regions of SARS-CoV-2 having shown high mutation rates in the past, a relatively stable T-cell response can be expected regarding new SARS-CoV-2 strains in the future. Analysis of the T-cell epitope landscape of SARS-CoV-2 suggests T-cell intrinsic factors as likely modulators of disease severity and that the capacity of MHC-peptide presentation remains stable among circulating SARS-CoV-2 viral strains.
Keywords: APC; HLA haplotypes; NetMHCpan; SARS‐CoV‐2; T‐cell immunity.