Binding affinities of 438 HLA proteins to complete proteomes of seven pandemic viruses and distributions of strongest and weakest HLA peptide binders in populations worldwide

Abstract

Funding information Australian Government Research Training Program Stipend (RTPS); AustralianWe report detailed peptide-binding affinities between 438 HLA Class I and Class II proteins and complete proteomes of seven pandemic human viruses, including coronaviruses, influenza viruses and HIV-1. We contrast these affinities with HLA allele frequencies across hundreds of human populations worldwide. Statistical modelling shows that peptide-binding affinities classified into four distinct categories depend on the HLA locus but that the type of virus is only a weak predictor, except in the case of HIV-1. Among the strong HLA binders (IC 50 ≤ 50), we uncovered 16 alleles (the top ones being A*02:02, B*15:03 and DRB1*01:02) binding more than 1% of peptides derived from all viruses, 9 (top ones including HLA-A*68:01, B*15:25, C*03:02 and DRB1*07:01)

Correlation of the two most frequent HLA haplotypes in the Italian population to the differential regional incidence of Covid-19

“…Very recent works employed different bioinformatic approaches to predict the best SARS-CoV-2 derived B and T cell epitopes and their associated HLA alleles, that may help to design effective vaccines and find protective antibodies [30][31][32][33][34][35]. Employing HLA binding affinity prediction tools, it has been observed that HLA-A and HLA-C alleles exhibited the relatively most and least capacity to present SARS-CoV-2 antigens, respectively.…”

Correlation of the two most frequent HLA haplotypes in the Italian population to the differential regional incidence of Covid-19

“…Very recent works employed different bioinformatic approaches to predict the best SARS-CoV-2 derived B and T cell epitopes and their associated HLA alleles, that may help to design effective vaccines and nd protective antibodies [21,[27][28][29][30][31]. Employing HLA binding a nity prediction tools, it has been observed that HLA-A and HLA-C alleles exhibited the relatively most and least capacity to present SARS-CoV-2 antigens, respectively.…”

HLA allele frequencies and susceptibility to COVID‐19 in a group of 99 Italian patients

“…Ongoing researches are trying to elucidate the mechanisms potentially responsible for inducing the immune response against SARS‐Cov‐2, including the role of HLA alleles in the affected individuals 4 . The HLA complex constitutes a specific group of molecules expressed on the cell surface, crucial for the recognition of nonself molecules by the acquired immune system.…”

“…[1][2][3] Ongoing researches are trying to elucidate the mechanisms potentially responsible for inducing the immune response against SARS-Cov-2, including the role of HLA alleles in the affected individuals. 4 The HLA complex constitutes a specific group of molecules expressed on the cell surface, crucial for the recognition of nonself molecules by the acquired immune system. Their essential function is to bind and display antigens derived from pathogens on the cell surface and present them to the appropriate T lymphocytes, triggering an immune response.…”

“…5,6 Different scientific contributions were recently published in the literature addressing the potential relevance of HLA polymorphism and susceptibility to pandemic viruses, with particular interest in the SARS-Cov-2 infection, focusing the attention on differences of HLA allele frequency and distribution of HLA peptide binders in populations. 4,[7][8][9][10] Up to date conflicting results were published in the Literature. A recent study by Ellinghaus et al, investigating a large cohort of COVID-19 patients from Italy and Spain, using a genome-wide association study approach, did not find any significant evidence of HLA involvement.…”