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

Publication date: Apr 02, 2024

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 4 point mutations in the hACE2-binding region RBD496-513 of Omicron B1.1.529 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.

Concepts Keywords
4endocrinology Class
August Cov
Biotech Epitopes
Germany Figure
Viral Haplotypes
Hla
Medrxiv
Omicron
Peptides
Preprint
Proteasome
Proteasomes
Rbd
Sars

(Visited 1 times, 1 visits today)