Human leukocyte antigen susceptibility map for SARS-CoV-2

Austin Nguyen; Julianne K David; Sean K Maden; Mary A Wood; Benjamin R Weeder; Abhinav Nellore; Reid F Thompson

To the best of our knowledge, this is the first study to evaluate per-allele viral proteome presentation across a wide range of HLA alleles using MHC-peptide binding affinity predictors. This study also introduces the relationship between coronavirus sequence conservation and MHC class I antigen presentation. We show that individual HLA, haplotype, and full genotype variability likely influence the capacity to respond to SARS-CoV-2 infection, and we note certain alleles in particular (e.g. HLA-B*46:01) that could be associated with more severe infection, as previously shown with SARS-CoV (1) . Indeed, we further compare SARS-CoV and SARS-CoV-2 peptide presentation and note a high degree of similarity between the two across HLA types. Finally, this is the first study to report global distributions of HLA types and haplotypes with potential epidemiological ramifications in the setting of the current pandemic. We found that in general, there is no correlation between the HLA allelic frequency in the population and allelic capacity to bind SARS-CoV or SARS-CoV-2 peptides, irrespective of estimated timing of peptide production during the viral replication cycle. While we are not aware of any studies explicitly reporting the relationship between human coronavirus epitope abundance and immune response, there is data in vaccinia virus that suggests that early peptide antigens are more likely to generate CD8+ T-cell responses while antibody and CD4+ T-cell responses are more likely to target later mRNA expression with higher peptide abundance in the virion (53) .