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Updated: May 23, 2025

Tumor Transplantation for Assessing the Dynamics of Tumor-Infiltrating CD8+ T Cells in Mice
Published on: June 12, 2021
Mutational pressure promotes release of public CD8+ T cell epitopes by proteasome from SARS-CoV-2 RBD of Omicron and
Anna A Kudriaeva1, Ivan O Butenko2, George A Saratov1
1Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow 117997, Russia.
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 human leukocyte antigen (HLA) class I molecules from 18,771 unique haplotypes of 28,104 individuals to 821 peptides experimentally observed from spike protein receptor binding domain (RBD) of five main SARS-CoV-2 strains hydrolyzed by human proteasomes with constitutive and immune catalytic phenotypes. Our data read that mutations in the human angiotensin-converting enzyme 2 (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 strains contain same amino acid substitutions at key proteasomal cleavage sites, thus preserving identified core epitopes.
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