Key Protein Mutations Affect COVID-19 Infection
Like all vertebrates, humans carry the MHC-I molecule in all nucleated cells. MHC-I is generally located on the surface of cells and can provide some conditions in general cells. MHC-I can be compared to a "billboard" for cells, which can show the synthesis of intracellular peptides (proteins) to CD8+ T cells. If the latter detects abnormalities (such as when a cell is infected with a virus, the virus protein will be presented to the cell surface by MHC-I molecules), CD8+ T cells will kill the cell.
However, MHC-I is a polymorphic molecule, which means that it exists in many forms, and their ability to bind viral fragments and to present to T cells are significantly different. Depending on the existing variants or alleles of MHC-I, the body may have a successful immune response to SARS-CoV-2, or it may not be successful, causing the body to become more vulnerable.
In a new study published in the journal Cell Reports Medicine, the authors describe a complex algorithm called EnsembleMHC, which aims to predict which MHC-I alleles best bind to viral fragments and present them to T cells . They also identified 108 viral peptides derived from SARS-CoV-2 structural proteins, which are considered to be effective immunogenic molecules.
The study examined 52 common MHC-I alleles and found significant differences in their ability to bind viral segments from the complete SARS-CoV-2 genome as well as segments from a critical structural subset of viral proteins considered to be the most important.
CD8+ T cells can recognize multiple epitopes of these structural proteins. When CD8+ T cells encounter these molecules, they usually target the infected cells for destruction.
When the researchers compared COVID-19 data from 23 countries, they found that the mortality of the disease was closely related to the distribution of MHC-I variants. Specifically, people with specific MHC-I alleles (SARS-CoV-2 peptide fragments have stronger binding capacity), show lower COVID-19 mortality, indicating these favorable MHC-I alleles Genes produce a powerful immune response when encountering a new type of coronavirus.
This work is of great significance for monitoring the vulnerability of individuals and populations to COVID-19, and can also help researchers to identify the important components of the SARS-CoV-2 pathogen that can most stimulate the immune response, which is the key to future vaccines section.
In addition, when comparing only those alleles that show high binding affinity to the S, N, M, and E proteins, the low COVID-19 mortality rate has the strongest association with this set of favorable MHC-I alleles. Once again It shows that the structural protein of the virus is the most effective in generating an immune response.
The results suggest that patients with an MHC-I allele that can bind to the SARS-CoV-2 structural protein peptide can stimulate an enhanced CD8+ T cell response and improve post-infection outcomes and reduce mortality.
The powerful technology described in this new study further reveals the subtle relationship between MHC-I alleles and immune responses, and will help researchers identify the most important immunogenic viral fragments in SARS-CoV-2 to Help future vaccine development. Combining this type of information with the patient's clinical data and genetic characteristics may help identify those who are still at greatest risk for this elusive disease.
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