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 explore the potential for a given HLA allele to produce an antiviral response, we assessed the HLA binding affinity of all possible 8-to 12-mers from the SARS-CoV-2 proteome (n=48,395 unique peptides). We then removed from further consideration 16,138 peptides that were not predicted to enter the MHC class I antigen processing pathway via proteasomal cleavage. For the remaining 32,257 peptides, we repeated binding affinity predictions for a total of 145 different HLA types, and we show here the SARS-CoV-2-specific distribution of per-allele proteome presentation (predicted binding affinity threshold <500nM, Figure 1 , Supplementary Table S1 ). Importantly, we note that the putative capacity for SARS-CoV-2 antigen presentation is unrelated to the HLA allelic frequency in the population (Figure 1 ). We identify HLA-B*46:01 as the HLA allele with the fewest predicted binding peptides for SARS-CoV-2. We performed the same analyses for the closely-related SARS-CoV proteome (Supplementary Figure S1 ) and similarly note that HLA-B*46:01 was predicted to present the fewest SARS-CoV peptides, keeping with previous clinical data associating this allele with severe disease (1) . Supplementary Table S1 ) that putatively bind to each of 145 HLA alleles is shown as a series of horizontal bars, with dark and light shading indicating the number of tightly (<50nM) and loosely (<500nM) binding peptides respectively, and with green, orange, and purple colors representing HLA-A, -B, and -C alleles, respectively. Alleles are sorted in descending order based on the number of peptides they bind (<500nM). The corresponding estimated allelic frequency in the global population is also shown (to left), with length of horizontal bar indicating absolute frequency in the population.