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Mutational pressure drives enhanced release of proteasome-generated public CD8+ T cell epitopes from SARS-CoV-2 RBD of Omicron and its current lineages

Kudriaeva, A. A.; Butenko, I. O.; Saratov, G. A.; Ri, M.; Mokrushina, Y. A.; Bondarev, A. A.; Evpak, A. S.; Smirnov, I. V.; Matyushkina, D. S.; Gabibov, A. G.; Govorun, V. M.; Belogurov, A. A.

2024-04-03 infectious diseases
10.1101/2024.04.03.24305074 medRxiv
Show abstract

The COVID-19 pandemic was the most dramatic in the newest history with nearly 7 million deaths and global impact on mankind. Here we report binding index of 305 HLA class I molecules from 18,771 unique haplotypes of 28,104 individuals to 821 peptides experimentally observed from spike protein RBD of 5 main SARS-CoV-2 strains hydrolyzed by human proteasomes with constitutive and immune catalytic phenotypes. Our data read that mutations in the hACE2-binding region RBD496-513 of Omicron B.1.1.529 strain results in a dramatic increase of proteasome-mediated release of two public HLA class I epitopes. Global population analysis of HLA class I haplotypes, specific to these peptides, demonstrated decreased mortality of human populations enriched in these haplotypes from COVID-19 after but not before December, 2021, when Omicron became dominant SARS-CoV-2 strain. Noteworthy, currently circulating BA.2.86 and JN.1 lineages contain no amino acid substitutions in RBD496-513 thus preserving identified core epitopes.

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