HLA-A*01:01 allele diminishing in COVID-19 patients population associated with non-structural epitope abundance in CD8+ T-cell repertoire

Maxim Shkurnikov; Stepan Nersisyan; Darya Averinskaya; Milena Chekova; Fedor Polyakov; Aleksei Titov; Dmitriy Doroshenko; Valery Vechorko; Alexander Tonevitsky

doi:10.7717/peerj.14707

HLA-A01:01* allele diminishing in COVID-19 patients population associated with non-structural epitope abundance in CD8+ T-cell repertoire

PeerJ. 2023 Jan 18:11:e14707. doi: 10.7717/peerj.14707. eCollection 2023.

Authors

Maxim Shkurnikov¹, Stepan Nersisyan^{1

2

3

4}, Darya Averinskaya¹, Milena Chekova¹, Fedor Polyakov¹, Aleksei Titov⁵, Dmitriy Doroshenko⁶, Valery Vechorko⁶, Alexander Tonevitsky^{1

4}

Affiliations

¹ Faculty of Biology and Biotechnology, HSE University, Moscow, Russia.
² Institute of Molecular Biology, The National Academy of Sciences of the Republic of Armenia, Yerevan, Armenia.
³ Armenian Bioinformatics Institute (ABI), Yerevan, Armenia.
⁴ Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, Russia.
⁵ National Research Center for Hematology, Moscow, Russia.
⁶ O.M. Filatov City Clinical Hospital, Moscow, Russia.

Abstract

In mid-2021, the SARS-CoV-2 Delta variant caused the third wave of the COVID-19 pandemic in several countries worldwide. The pivotal studies were aimed at studying changes in the efficiency of neutralizing antibodies to the spike protein. However, much less attention was paid to the T-cell response and the presentation of virus peptides by MHC-I molecules. In this study, we compared the features of the HLA-I genotype in symptomatic patients with COVID-19 in the first and third waves of the pandemic. As a result, we could identify the diminishing of carriers of the HLA-A*01:01 allele in the third wave and demonstrate the unique properties of this allele. Thus, HLA-A*01:01-binding immunoprevalent epitopes are mostly derived from ORF1ab. A set of epitopes from ORF1ab was tested, and their high immunogenicity was confirmed. Moreover, analysis of the results of single-cell phenotyping of T-cells in recovered patients showed that the predominant phenotype in HLA-A*01:01 carriers is central memory T-cells. The predominance of T-lymphocytes of this phenotype may contribute to forming long-term T-cell immunity in carriers of this allele. Our results can be the basis for highly effective vaccines based on ORF1ab peptides.

Keywords: COVID-19; ELISpot; HLA-A*01:01; MHC-I; T-cell immune response.

MeSH terms

Alleles
CD8-Positive T-Lymphocytes
COVID-19*
Epitopes, T-Lymphocyte
HLA-A Antigens
Humans
Pandemics / prevention & control
SARS-CoV-2 / metabolism

Substances

Epitopes, T-Lymphocyte
HLA-A Antigens

Supplementary concepts

SARS-CoV-2 variants

Grants and funding

The research was performed within the framework of the “Creation of Experimental Laboratories in the Natural Sciences Program” at the HSE University. Funding for open access charge was provided by the Laboratory for Research on Molecular Mechanisms of Longevity, HSE University. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.