1. Individual HLA-A, -B, -C, and -DRB1 Genotypes Are No Major Factors Which Determine COVID-19 Severity
- Author
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Schetelig, Johannes, Heidenreich, Falk, Baldauf, Henning, Trost, Sarah, Falk, Bose, Hoßbach, Christian, Real, Ruben, Roers, Axel, Lindemann, Dirk, Dalpke, Alexander, Kolditz, Martin, de With, Katja, Bornhäuser, Martin, Bonifacio, Ezio E., Rücker-Braun, Elke, Lange, Vinzenz, Markert, Jan, Barth, Ralf, Hofmann, Jan A., Sauter, Jürgen, Bernas, Stefanie N., and Schmidt, Alexander H.
- Subjects
Adult ,Male ,Genotype ,in silico prediction ,SARS-CoV-2 ,Histocompatibility Antigens Class I ,Immunology ,T-cell epitopes ,Histocompatibility Antigens Class II ,Epitopes, T-Lymphocyte ,Middle Aged ,HLA ,immunogenetics ,Cross-Sectional Studies ,Spike Glycoprotein, Coronavirus ,Humans ,Immunology and Allergy ,Computer Simulation ,Female ,Coronavirus Infections ,Original Research - Abstract
HLA molecules are key restrictive elements to present intracellular antigens at the crossroads of an effective T-cell response against SARS-CoV-2. To determine the impact of the HLA genotype on the severity of SARS-CoV-2 courses, we investigated data from 6,919 infected individuals. HLA-A, -B, and -DRB1 allotypes grouped into HLA supertypes by functional or predicted structural similarities of the peptide-binding grooves did not predict COVID-19 severity. Further, we did not observe a heterozygote advantage or a benefit from HLA diplotypes with more divergent physicochemical peptide-binding properties. Finally, numbers of in silico predicted viral T-cell epitopes did not correlate with the severity of SARS-CoV-2 infections. These findings suggest that the HLA genotype is no major factor determining COVID-19 severity. Moreover, our data suggest that the spike glycoprotein alone may allow for abundant T-cell epitopes to mount robust T-cell responses not limited by the HLA genotype.
- Published
- 2021
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