The SARS-CoV-2 delta variant that caused the third wave of COVID-19 in mid-2021 was found to be more infectious than previous SARS-CoV-2 variants. In addition, protein mutations in the delta variant have been found to significantly reduce the effect of humoral immunity acquired on COVID-19 from previous infection or vaccination.
Acquired immunity to infection is largely provided by T lymphocytes – cells of the immune system that detect foreign antigens after infection and trigger the immune response. This is the role of T-cell receptors (or TCRs), which are special receptors on the T-cell surface.
TCRs are responsible for pathogen recognition. They can “remember” specific antigens encountered previously and mount a faster immune response next time, thus protecting the body from reinfection with the same virus.
Human leukocyte antigen class I (HLA-I) molecules help recognize pathogens. HLA-I molecules bind to pathogen molecules and present them on the infected cell surface, where they can be recognized by T-cell receptors.
An individual’s set of HLA-I genes is unique. This is the main reason why viral infections can strike people with varying degrees of severity. In particular, as HSE researchers have previously shown, an individual’s HLA-I genotype determines predisposition to severe forms of COVID-19.
So far, however, patients’ genotypes have only been studied in distinct waves of the coronavirus pandemic. Since then, both the virus and people’s susceptibility to it have changed dramatically.
The researchers compared the HLA-I genotypes of COVID-19 patients in the first and third waves of the pandemic. The genomes of COVID-19 patients were analysed, including 147 patients from the first wave (between May and August 2020) and 219 patients from the third wave (between June and July 2021).
The researchers performed HLA typing by means of next generation sequencing (NGS) which identifies different forms of genes (alleles) in a given individual. The scientists then compared the frequency of occurrence of alleles between groups of patients.
They found half as many patients had the HLA-A*1:1 allele in the third wave as in the first wave. Other variants of HLA-I genes were equally common in both groups.
Previously, the HLA-A*01:01 allele was thought to be associated with a higher risk of infection and a severe course of COVID-19. But the researchers now suggest that this allele may be more beneficial than previously thought. The fact that it occurs less frequently among third-wave patients may indicate that carriers of this allele have developed strong T-cell immunity against COVID-19.
HLA-A*01:01 mainly binds to peptides originating from the ORF1ab region of the SARS-CoV-2 genome. ORF1ab is a conservative part of the genome, which means that it is less prone to mutations than other regions. Presumably, the immune systems of HLA-A* 01:01 carriers learned how to detect COVID-19 despite the mutations.
“Earlier, we showed that carriers of HLA-A* 01:01 are at increased risk of severe COVID-19. However, a significant proportion of patients, including carriers of HLA-A* 01:01, have a mild form Or even without symptoms of COVID-19, ”explains the head of the HSE Laboratory for Research on Molecular Mechanisms of Longevity Maxim Shkurnikov.
“The reason we found a decrease in the number of carriers of this allele among the third wave patients may be that a significant number of these patients had already been infected by the time the third wave hit and had built up strong T-cell immunity, allowing them to avoid hospitalization this time around.”
In addition, so-called memory T cells predominate in former COVID-19 patients who have the HLA-A*01:01 allele; These cells store information about the infection long after it has been eliminated, allowing them to mount a rapid immune response upon re-exposure.
The paper has been published in the journal Berg.
The study results indicate that the immune systems of carriers of the 01:01 HLA-A* allele tend to be more effective at remembering and recognizing COVID-19 regardless of its mutations. This confirms the possibility of genetic susceptibility to severe COVID-19. These findings could also inform the development of effective COVID-19 vaccines that target the ORF1ab genome region.
Maxim Shkurnikov et al, HLA-A*01:01 allele diminution in a cohort of COVID-19 patients associated with nonstructural epitope overabundance in the CD8+ T-cell repertoire, Berg (2023). DOI: 10.7717 / peerj.14707 On medRxiv: www.medrxiv.org/content/10.110… 022.07.05.22277214v2
Provided by the National Research University Higher School of Economics
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