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.
Keywords: CD8; EnsembleMHC; MHC-I; SARS-CoV-2; epitope; immunoinformatics; population dynamics; risk.
【저자키워드】 SARS-CoV-2, risk, CD8, Population dynamics, immunoinformatics, epitope, EnsembleMHC, MHC-I, 【초록키워드】 Mortality, Immunity, Infection, alleles, peptide, risk, virus, E protein, T cell, immune responses, Algorithm, peptides, structural protein, mortality rate, MHC, binding, association, Frequency, computation, human population, Candidates, Consensus, inverse correlation, protein sequence, driving, starting, Affect, Alter, predicted, significantly, Potential, highlighting, 【제목키워드】 Mortality, epitope, predicted, Total,