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.
- population dynamics
ASJC Scopus subject areas
- Biochemistry, Genetics and Molecular Biology(all)