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  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

Barquera, R., Collen, E., Di, D., Buhler, S., Teixeira, J., Llamas, B., et al. (2020). 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. HLA Immune Response Genetics, 96(3): 13956, pp. 277-298. doi:10.1111/tan.13956.

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Free Access on Wiley Online Library (Publisher version)
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(last checked: Nov. 2020)
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Data S1-S7; Table S1-S4 (Supplementary material)
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PDF files. - Table S1: Number of population samples tested for HLA per locus and geographic region ; Table S2: Detailed list of population samples used in this study ; Table S3: List of alleles used in this study ; Table S4: List of strongest and weakest HLA binders for all viruses. - (last checked Nov. 2020)

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 Creators:
Barquera, Rodrigo1, Author              
Collen, Evelyn, Author
Di, Da, Author
Buhler, Stéphane, Author
Teixeira, João, Author
Llamas, Bastien, Author
Nunes, José Manuel, Author
Sanchez-Mazas, Alicia, Author
Affiliations:
1Archaeogenetics, Max Planck Institute for the Science of Human History, Max Planck Society, ou_2074310              

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Free keywords: Coronavirus, COVID-19, HIV, HLA population genetics, Indigenous Americans, influenza, natural selection, peptide binding predictions, SARS-CoV-2
 Abstract: We 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. Amongst the strong HLA binders (IC50 ≤?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) binding all viruses except HIV-1, and 15 (top ones A*02:01 and C*14:02) only binding coronaviruses. The frequencies of strongest and weakest HLA peptide binders differ significantly among populations from different geographic regions, with Indigenous peoples of America showing both higher frequencies of strongest and lower frequencies of weakest binders. As many HLA proteins are strong binders of peptides from distinct viral families, we discuss this result in relation to possible signatures of natural selection on HLA promiscuous alleles due to undetermined past pathogenic infections. Although highly relevant for evolutionary genetics and the development of vaccine therapies, these results should not lead to forget that individual resistance and vulnerability to diseases go beyond the sole HLA allelic affinity and depend on multiple, complex and often unknown biological, environmental and other variables. This article is protected by copyright. All rights reserved.

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Language(s): eng - English
 Dates: 2020-05-312020-09
 Publication Status: Published in print
 Pages: 22
 Publishing info: -
 Table of Contents: 1 Introduction

2 Material and methods
2.1 Population samples
2.2 HLA alleles and proteins
2.3 Viral proteins
2.3.1 SARS-CoV-1
2.3.2 SARS-CoV-2
2.3.3 MERS-CoV
2.3.4 A/H1N1
2.3.5 A/H3N2
2.3.6 A/H7N9
2.3.7 HIV-1
2.4 HLA peptide-binding affinity predictions

3 Statistical analyses
3.1 HLA strongest and weakest binders of SARS-CoV-2 peptides in populations worldwide
3.2 HLA strongest and weakest binders of peptides derived from the seven viruses

4 Results
4.1 Binding affinities of HLA-A, -B, -C, -DR and -DQ molecules to SARS-CoV-2
4.2 List of strongest and weakest HLA SARS-CoV-2 peptide binders at each HLA locus
4.2.1 HLA-A
4.2.2 HLA-B
4.2.3 HLA-C
4.2.4 HLA-DR
4.2.5 HLA-DQ
4.3 Global frequency distributions of strongest and weakest HLA SARS-CoV-2 peptide binders
4.4 Effects of HLA locus and geographic region on the global frequency
distributions of HLA SARS-CoV-2 peptide binders
4.5 Comparison of the HLA peptidebinding patterns observed for the seven different viruses
4.6 Effects of the kind of binding, the HLA locus and the variety of virus on the proportions of bound peptides

5 Discussion
5.1 Binding affinities of HLA proteins to SARS-CoV-2 and comparison to other viruses
5.2 Global distribution of strongest and weakest HLA SARS-CoV-2 peptide binders in human populations

6 Conclusion
 Rev. Type: Peer
 Identifiers: DOI: 10.1111/tan.13956
Other: shh2618
 Degree: -

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Title: HLA Immune Response Genetics
  Abbreviation : HLA
Source Genre: Journal
 Creator(s):
Affiliations:
Publ. Info: Wiley
Pages: - Volume / Issue: 96 (3) Sequence Number: 13956 Start / End Page: 277 - 298 Identifier: Other: 2059-2310
CoNE: https://pure.mpg.de/cone/journals/resource/2059-2302