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

Frontiers in Immunology

卷:13

Da Di¹  Seyed Hamid Hashemi²  Fariba Keramat²  Mojgan Mamani²  Peyman Eini²  Mohammad Mahdi Majzoobi²  Samaneh Ebrahimi³  Ghasem Solgi³  Mina Noroozbeygi³  Hamid Reza Ghasemi Basir⁴  Saeed Alizadeh⁵ 

[1] Anthropology Unit, Department of Genetics and Evolution, University of Geneva, Geneva, Switzerland;

[2] Brucellosis Research Centre, Hamadan University of Medical Sciences, Hamadan, Iran;

[3] Department of Immunology, School of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran;

[4] Department of Pathology, School of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran;

[5] Department of Radiology, School of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran;

关键词: COVID-19;    HLA;    overall binding repertoire;    SARS-CoV-2-derived peptides;    HLA binding prediction;   

DOI  :  10.3389/fimmu.2022.891816

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown