Abstract
Polymorphisms in MHC-I protein sequences across human populations significantly affect viral peptide binding capacity, and thus alter T cell immunity to infection. In the present study, we assess the relationship between observed SARS-CoV-2 population mortality and the predicted viral binding capacities of 52 common MHC-I alleles. Potential SARS-CoV-2 MHC-I peptides are identified using a consensus MHC-I binding and presentation prediction algorithm called EnsembleMHC. Starting with nearly 3.5 million candidates, we resolve a few hundred highly probable MHC-I peptides. By weighing individual MHC allele-specific SARS-CoV-2 binding capacity with population frequency in 23 countries, we discover a strong inverse correlation between predicted population SARS-CoV-2 peptide binding capacity and mortality rate. Our computations reveal that peptides derived from the structural proteins of the virus produce a stronger association with observed mortality rate, highlighting the importance of S, N, M, and E proteins in driving productive immune responses. Wilson et al. define a predicted MHC allele-specific hierarchy for the presentation of peptides derived from SARS-CoV-2 viral proteins. They find that a composite population-level metric combining predicted MHC allele SARS-CoV-2 binding capacity and endemic allele frequencies is inversely correlated with deaths per million.
Original language | English (US) |
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Article number | 100221 |
Journal | Cell Reports Medicine |
Volume | 2 |
Issue number | 3 |
DOIs | |
State | Published - Mar 16 2021 |
Keywords
- CD8
- EnsembleMHC
- MHC-I
- SARS-CoV-2
- epitope
- immunoinformatics
- population dynamics
- risk
ASJC Scopus subject areas
- General Biochemistry, Genetics and Molecular Biology