tetano
Editor, Senior Moderator
Front Immunol
. 2024 May 9:15:1357731.
doi: 10.3389/fimmu.2024.1357731. eCollection 2024. A bioinformatic analysis of T-cell epitope diversity in SARS-CoV-2 variants: association with COVID-19 clinical severity in the United States population
Grace J Kim[SUP] 1 2 [/SUP], Jacob H Elnaggar[SUP] 2 3 [/SUP], Mallory Varnado[SUP] 2 [/SUP], Amy K Feehan[SUP] 4 [/SUP], Darlene Tauzier[SUP] 5 [/SUP], Rebecca Rose[SUP] 6 [/SUP], Susanna L Lamers[SUP] 6 [/SUP], Maya Sevalia[SUP] 2 [/SUP], Najah Nicholas[SUP] 2 [/SUP], Elizabeth Gravois[SUP] 5 [/SUP], Daniel Fort[SUP] 4 [/SUP], Judy S Crabtree[SUP] 1 [/SUP], Lucio Miele[SUP] 1 [/SUP]
Affiliations
Long-term immunity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) requires the identification of T-cell epitopes affecting host immunogenicity. In this computational study, we explored the CD8[SUP]+[/SUP] epitope diversity estimated in 27 of the most common HLA-A and HLA-B alleles, representing most of the United States population. Analysis of 16 SARS-CoV-2 variants [B.1, Alpha (B.1.1.7), five Delta (AY.100, AY.25, AY.3, AY.3.1, AY.44), and nine Omicron (BA.1, BA.1.1, BA.2, BA.4, BA.5, BQ.1, BQ.1.1, XBB.1, XBB.1.5)] in analyzed MHC class I alleles revealed that SARS-CoV-2 CD8[SUP]+[/SUP] epitope conservation was estimated at 87.6%-96.5% in spike (S), 92.5%-99.6% in membrane (M), and 94.6%-99% in nucleocapsid (N). As the virus mutated, an increasing proportion of S epitopes experienced reduced predicted binding affinity: 70% of Omicron BQ.1-XBB.1.5 S epitopes experienced decreased predicted binding, as compared with ~3% and ~15% in the earlier strains Delta AY.100-AY.44 and Omicron BA.1-BA.5, respectively. Additionally, we identified several novel candidate HLA alleles that may be more susceptible to severe disease, notably HLA-A*32:01, HLA-A*26:01, and HLA-B*53:01, and relatively protected from disease, such as HLA-A*31:01, HLA-B*40:01, HLA-B*44:03, and HLA-B*57:01. Our findings support the hypothesis that viral genetic variation affecting CD8 T-cell epitope immunogenicity contributes to determining the clinical severity of acute COVID-19. Achieving long-term COVID-19 immunity will require an understanding of the relationship between T cells, SARS-CoV-2 variants, and host MHC class I genetics. This project is one of the first to explore the SARS-CoV-2 CD8[SUP]+[/SUP] epitope diversity that putatively impacts much of the United States population.
Keywords: CD8 T cell epitope; COVID-19; HLA; SARS-CoV-2; T cell epitope; bioinformatics; vaccine design.
. 2024 May 9:15:1357731.
doi: 10.3389/fimmu.2024.1357731. eCollection 2024. A bioinformatic analysis of T-cell epitope diversity in SARS-CoV-2 variants: association with COVID-19 clinical severity in the United States population
Grace J Kim[SUP] 1 2 [/SUP], Jacob H Elnaggar[SUP] 2 3 [/SUP], Mallory Varnado[SUP] 2 [/SUP], Amy K Feehan[SUP] 4 [/SUP], Darlene Tauzier[SUP] 5 [/SUP], Rebecca Rose[SUP] 6 [/SUP], Susanna L Lamers[SUP] 6 [/SUP], Maya Sevalia[SUP] 2 [/SUP], Najah Nicholas[SUP] 2 [/SUP], Elizabeth Gravois[SUP] 5 [/SUP], Daniel Fort[SUP] 4 [/SUP], Judy S Crabtree[SUP] 1 [/SUP], Lucio Miele[SUP] 1 [/SUP]
Affiliations
- PMID: 38784379
- PMCID: PMC11112498
- DOI: 10.3389/fimmu.2024.1357731
Long-term immunity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) requires the identification of T-cell epitopes affecting host immunogenicity. In this computational study, we explored the CD8[SUP]+[/SUP] epitope diversity estimated in 27 of the most common HLA-A and HLA-B alleles, representing most of the United States population. Analysis of 16 SARS-CoV-2 variants [B.1, Alpha (B.1.1.7), five Delta (AY.100, AY.25, AY.3, AY.3.1, AY.44), and nine Omicron (BA.1, BA.1.1, BA.2, BA.4, BA.5, BQ.1, BQ.1.1, XBB.1, XBB.1.5)] in analyzed MHC class I alleles revealed that SARS-CoV-2 CD8[SUP]+[/SUP] epitope conservation was estimated at 87.6%-96.5% in spike (S), 92.5%-99.6% in membrane (M), and 94.6%-99% in nucleocapsid (N). As the virus mutated, an increasing proportion of S epitopes experienced reduced predicted binding affinity: 70% of Omicron BQ.1-XBB.1.5 S epitopes experienced decreased predicted binding, as compared with ~3% and ~15% in the earlier strains Delta AY.100-AY.44 and Omicron BA.1-BA.5, respectively. Additionally, we identified several novel candidate HLA alleles that may be more susceptible to severe disease, notably HLA-A*32:01, HLA-A*26:01, and HLA-B*53:01, and relatively protected from disease, such as HLA-A*31:01, HLA-B*40:01, HLA-B*44:03, and HLA-B*57:01. Our findings support the hypothesis that viral genetic variation affecting CD8 T-cell epitope immunogenicity contributes to determining the clinical severity of acute COVID-19. Achieving long-term COVID-19 immunity will require an understanding of the relationship between T cells, SARS-CoV-2 variants, and host MHC class I genetics. This project is one of the first to explore the SARS-CoV-2 CD8[SUP]+[/SUP] epitope diversity that putatively impacts much of the United States population.
Keywords: CD8 T cell epitope; COVID-19; HLA; SARS-CoV-2; T cell epitope; bioinformatics; vaccine design.