Influence of HLA class II polymorphism on predicted cellular immunity against SARS-CoV-2 at the population and individual level

Copley, Hannah C; Gragert, Loren; Leach, Andrew R; Kosmoliaptsis, Vasilis

Development of effective adaptive immune responses after coronavirus disease 2019 (COVID-19) and after vaccination against SARS-CoV-2 is predicated on recognition of viral peptides, presented in the context of HLA class II molecules, by CD4+ T-cells. We capitalised on extensive high resolution HLA data deposited in the National Marrow Donor Program registry to obtain detailed information on human HLA haplotype frequencies of twenty five human populations and used a bioinformatics approach to investigate the role of HLA polymorphism on SARS-CoV-2 immunogenicity at the population and at the individual level. Within populations, we identify wide inter-individual variability in predicted CD4+ T-cell reactivity against structural, non-structural and accessory SARS-CoV-2 proteins, according to expressed HLA genotype. However, we find similar potential for anti-SARS-CoV-2 cellular immunity at the population level, across all ethnic groups examined, suggesting that HLA polymorphism is unlikely to account for observed disparities in clinical outcomes after COVID-19 among different race and ethnic groups. We predict robust immune reactivity against SARS-CoV-2 Spike protein, the basis for the majority of current vaccination efforts, both at the population and individual level, despite significant variation in Spike-derived peptide presentation by individual HLA genotypes. Finally, we provide comprehensive maps of SARS-CoV-2 proteome immunogenicity accounting for population coverage in major ethnic groups. Our findings provide important insight on the potential role of HLA polymorphism on development of protective immunity after SARS-CoV-2 infection and after vaccination and a firm basis for further experimental studies in this field.