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.
Highlights
T-cell recognition is central for the adaptive immune response to a new challenge such as SARSCoV-2
In a generally healthy working age population of 6,919 individuals who had recovered from SARS-CoV-2 infections we found no associations of specific HLA genotypes with the severity of the acute clinical course
After correcting for multiple testing, we did not find significant associations of single allotypes with COVID-19 severity. These results suggest that individual HLA genotypes do not limit the immune response to SARS-CoV-2 infection as presumed by other studies [14,15,16, 36]
Summary
T-cell recognition is central for the adaptive immune response to a new challenge such as SARSCoV-2. Presentation of viral peptides on HLA molecules is an essential step required for adaptive immunity to the virus and critically determines the clinical course [1,2,3,4]. Multiple SARS-CoV-2 derived HLA class I and class II presented peptides have been identified and characterized as potential Tcell epitopes [3, 6, 7]. Certain SARSCoV-2 peptides elicit memory T-cell responses even in unexposed individuals [3]. These data provide a hint to crossreactive T-cell immunity between SARS-CoV-2 and ‘common cold’ coronaviruses, including human coronavirus (HCoV)OC43, HCoV-229E, HCoV-NL63, and HCoV-HKU1 [3, 8, 9]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
