Human leukocyte antigen susceptibility map for SARS-CoV-2

We probe how genetic variability across the three major histocompatibility complex (MHC) class I genes(human leukocyte antigen [HLA] A, B, and C) may affect susceptibility to and severity of severe acuterespiratory syndrome 2 (SARS-CoV-2), the virus responsible for coronavirus disease 2019 (COVID-19). Weexecute a comprehensive ​in silico​ analysis of viral peptide-MHC class I binding affinity across all known HLA-A, -B, and -C genotypes for all SARS-CoV-2 peptides. We further explore the potential for cross-protectiveimmunity conferred by prior exposure to four common human coronaviruses. The SARS-CoV-2 proteome issuccessfully sampled and presented by a diversity of HLA alleles. However, we found that HLA-B*46:01 hadthe fewest predicted binding peptides for SARS-CoV-2, suggesting individuals with this allele may beparticularly vulnerable to COVID-19, as they were previously shown to be for SARS ​(1)​. Conversely, we foundthat HLA-B*15:03 showed the greatest capacity to present highly conserved SARS-CoV-2 peptides that areshared among common human coronaviruses, suggesting it could enable cross-protective T-cell basedimmunity. Finally, we report global distributions of HLA types with potential epidemiological ramifications in thesetting of the current pandemic.