Total predicted MHC-I epitope load is inversely associated with population mortality from SARS-CoV-2

Eric A. Wilson, Gabrielle Hirneise, Abhishek Singharoy, Karen S. Anderson

Research output: Contribution to journalArticlepeer-review

11 Scopus citations


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 languageEnglish (US)
Article number100221
JournalCell Reports Medicine
Issue number3
StatePublished - Mar 16 2021


  • CD8
  • EnsembleMHC
  • MHC-I
  • SARS-CoV-2
  • epitope
  • immunoinformatics
  • population dynamics
  • risk

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)


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