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Susceptibility and Severity of COVID-19 Are Both Associated With Lower Overall Viral–Peptide Binding Repertoire of HLA Class I Molecules, Especially in Younger People

An important number of studies have been conducted on the potential association between human leukocyte antigen (HLA) genes and COVID-19 susceptibility and severity since the beginning of the pandemic. However, case–control and peptide-binding prediction methods tended to provide inconsistent conclu...

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Autores principales: Basir, Hamid Reza Ghasemi, Majzoobi, Mohammad Mahdi, Ebrahimi, Samaneh, Noroozbeygi, Mina, Hashemi, Seyed Hamid, Keramat, Fariba, Mamani, Mojgan, Eini, Peyman, Alizadeh, Saeed, Solgi, Ghasem, Di, Da
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9331187/
https://www.ncbi.nlm.nih.gov/pubmed/35911710
http://dx.doi.org/10.3389/fimmu.2022.891816
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author Basir, Hamid Reza Ghasemi
Majzoobi, Mohammad Mahdi
Ebrahimi, Samaneh
Noroozbeygi, Mina
Hashemi, Seyed Hamid
Keramat, Fariba
Mamani, Mojgan
Eini, Peyman
Alizadeh, Saeed
Solgi, Ghasem
Di, Da
author_facet Basir, Hamid Reza Ghasemi
Majzoobi, Mohammad Mahdi
Ebrahimi, Samaneh
Noroozbeygi, Mina
Hashemi, Seyed Hamid
Keramat, Fariba
Mamani, Mojgan
Eini, Peyman
Alizadeh, Saeed
Solgi, Ghasem
Di, Da
author_sort Basir, Hamid Reza Ghasemi
collection PubMed
description An important number of studies have been conducted on the potential association between human leukocyte antigen (HLA) genes and COVID-19 susceptibility and severity since the beginning of the pandemic. However, case–control and peptide-binding prediction methods tended to provide inconsistent conclusions on risk and protective HLA alleles, whereas some researchers suggested the importance of considering the overall capacity of an individual’s HLA Class I molecules to present SARS-CoV-2-derived peptides. To close the gap between these approaches, we explored the distributions of HLA-A, -B, -C, and -DRB1 1st-field alleles in 142 Iranian patients with COVID-19 and 143 ethnically matched healthy controls, and applied in silico predictions of bound viral peptides for each individual’s HLA molecules. Frequency comparison revealed the possible predisposing roles of HLA-A*03, B*35, and DRB1*16 alleles and the protective effect of HLA-A*32, B*58, B*55, and DRB1*14 alleles in the viral infection. None of these results remained significant after multiple testing corrections, except HLA-A*03, and no allele was associated with severity, either. Compared to peptide repertoires of individual HLA molecules that are more likely population-specific, the overall coverage of virus-derived peptides by one’s HLA Class I molecules seemed to be a more prominent factor associated with both COVID-19 susceptibility and severity, which was independent of affinity index and threshold chosen, especially for people under 60 years old. Our results highlight the effect of the binding capacity of different HLA Class I molecules as a whole, and the more essential role of HLA-A compared to HLA-B and -C genes in immune responses against SARS-CoV-2 infection.
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spelling pubmed-93311872022-07-29 Susceptibility and Severity of COVID-19 Are Both Associated With Lower Overall Viral–Peptide Binding Repertoire of HLA Class I Molecules, Especially in Younger People Basir, Hamid Reza Ghasemi Majzoobi, Mohammad Mahdi Ebrahimi, Samaneh Noroozbeygi, Mina Hashemi, Seyed Hamid Keramat, Fariba Mamani, Mojgan Eini, Peyman Alizadeh, Saeed Solgi, Ghasem Di, Da Front Immunol Immunology An important number of studies have been conducted on the potential association between human leukocyte antigen (HLA) genes and COVID-19 susceptibility and severity since the beginning of the pandemic. However, case–control and peptide-binding prediction methods tended to provide inconsistent conclusions on risk and protective HLA alleles, whereas some researchers suggested the importance of considering the overall capacity of an individual’s HLA Class I molecules to present SARS-CoV-2-derived peptides. To close the gap between these approaches, we explored the distributions of HLA-A, -B, -C, and -DRB1 1st-field alleles in 142 Iranian patients with COVID-19 and 143 ethnically matched healthy controls, and applied in silico predictions of bound viral peptides for each individual’s HLA molecules. Frequency comparison revealed the possible predisposing roles of HLA-A*03, B*35, and DRB1*16 alleles and the protective effect of HLA-A*32, B*58, B*55, and DRB1*14 alleles in the viral infection. None of these results remained significant after multiple testing corrections, except HLA-A*03, and no allele was associated with severity, either. Compared to peptide repertoires of individual HLA molecules that are more likely population-specific, the overall coverage of virus-derived peptides by one’s HLA Class I molecules seemed to be a more prominent factor associated with both COVID-19 susceptibility and severity, which was independent of affinity index and threshold chosen, especially for people under 60 years old. Our results highlight the effect of the binding capacity of different HLA Class I molecules as a whole, and the more essential role of HLA-A compared to HLA-B and -C genes in immune responses against SARS-CoV-2 infection. Frontiers Media S.A. 2022-07-07 /pmc/articles/PMC9331187/ /pubmed/35911710 http://dx.doi.org/10.3389/fimmu.2022.891816 Text en Copyright © 2022 Basir, Majzoobi, Ebrahimi, Noroozbeygi, Hashemi, Keramat, Mamani, Eini, Alizadeh, Solgi and Di https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Basir, Hamid Reza Ghasemi
Majzoobi, Mohammad Mahdi
Ebrahimi, Samaneh
Noroozbeygi, Mina
Hashemi, Seyed Hamid
Keramat, Fariba
Mamani, Mojgan
Eini, Peyman
Alizadeh, Saeed
Solgi, Ghasem
Di, Da
Susceptibility and Severity of COVID-19 Are Both Associated With Lower Overall Viral–Peptide Binding Repertoire of HLA Class I Molecules, Especially in Younger People
title Susceptibility and Severity of COVID-19 Are Both Associated With Lower Overall Viral–Peptide Binding Repertoire of HLA Class I Molecules, Especially in Younger People
title_full Susceptibility and Severity of COVID-19 Are Both Associated With Lower Overall Viral–Peptide Binding Repertoire of HLA Class I Molecules, Especially in Younger People
title_fullStr Susceptibility and Severity of COVID-19 Are Both Associated With Lower Overall Viral–Peptide Binding Repertoire of HLA Class I Molecules, Especially in Younger People
title_full_unstemmed Susceptibility and Severity of COVID-19 Are Both Associated With Lower Overall Viral–Peptide Binding Repertoire of HLA Class I Molecules, Especially in Younger People
title_short Susceptibility and Severity of COVID-19 Are Both Associated With Lower Overall Viral–Peptide Binding Repertoire of HLA Class I Molecules, Especially in Younger People
title_sort susceptibility and severity of covid-19 are both associated with lower overall viral–peptide binding repertoire of hla class i molecules, especially in younger people
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9331187/
https://www.ncbi.nlm.nih.gov/pubmed/35911710
http://dx.doi.org/10.3389/fimmu.2022.891816
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