SARS-CoV-2 Mutation Detail Information

Virus Mutation SARS-CoV-2 Mutation L452R


Basic Characteristics of Mutations
Mutation Site L452R
Mutation Site Sentence Although HLA-DPB1*02:02-restricted CD4+ Th cells did not response to some peptides with the L452R and L452Q mutations, the other CD4+ Th cells were not affected by any mutant peptides.
Mutation Level Amino acid level
Mutation Type Nonsynonymous substitution
Gene/Protein/Region S
Standardized Encoding Gene S  
Genotype/Subtype -
Viral Reference -
Functional Impact and Mechanisms
Disease Cell line    
Immune -
Target Gene -
Clinical and Epidemiological Correlations
Clinical Information -
Treatment -
Location -
Literature Information
PMID 37809871
Title SARS-CoV-2 spike protein-derived immunogenic peptides that are promiscuously presented by several HLA-class II molecules and their potential for inducing acquired immunity
Author Yajima Y,Kosaka A,Ohkuri T,Hirohashi Y,Li D,Nagasaki T,Nagato T,Torigoe T,Kobayashi H
Journal Heliyon
Journal Info 2023 Sep 20;9(9):e20192
Abstract The current coronavirus disease 2019 (COVID-19) pandemic that is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has a significant threat to public health. Although vaccines based on the mRNA of the SARS-CoV-2 spike protein have been developed to induce both cellular and humoral immunity against SARS-CoV-2, there have been some concerns raised about their high cost, particularly in developing countries. In the present study, we aim to identify an immunogenic peptide in the SARS-CoV-2 spike protein to activate cellular immunity, particularly CD4(+) helper T lymphocytes (Th cells), which are a commander of immune system. SARS-CoV-2 spike protein-derived peptides Spike(448-477) and Spike(489-513(N501Y))-specific CD4(+) Th cell lines were generated by repetitive stimulation of healthy donor-derived CD4(+)T-cells with each peptide. Their HLA-restrictions were addressed by using blocking antibodies against HLA and HLA-transfected L-cells. The epitopes of Spike(448-477)-specific CD4(+) Th cell lines were defined using a series of 7-14-mer overlapping truncated peptides and alanine-substituted epitope peptides. To address responsiveness of these CD4(+) Th cell lines to several SARS-CoV-2 variants, we stimulated the CD4(+) Th cell lines with mutated peptides. We addressed whether these identified peptides were useful for monitoring T-cell-based immune responses in vaccinated donors using the IFN-gamma ELISpot assay. The Spike(448-477) peptide was found to be a promiscuous peptide presented by HLA- DRB1*08:02, DR53, and DPB1*02:02. Although HLA-DPB1*02:02-restricted CD4(+) Th cells did not response to some peptides with the L452R and L452Q mutations, the other CD4(+) Th cells were not affected by any mutant peptides. We developed two tetramers to detect HLA-DRB1*08:02/Spike(449-463)- and Spike(449-463)(L452R/Y453F)-recognizing CD4(+) Th cells. Spike(489-513(N501Y)) peptide was also a promiscuously presented to HLA-DRB1*09:01 and DRB1*15:02. The T-cell responses specific to both peptides Spike(448-477) and Spike(489-513) were detected in PBMCs after vaccinations. In addition, we observed that the Spike(448-477) peptide activated both CD8(+) T-cells and CD4(+) Th cells in individuals receiving mRNA vaccines. SARS-CoV-2 spike protein-derived peptides, Spike(448-477) and Spike(489-513), include several epitopes that are presented by multiple HLA-class II alleles to activate CD4(+) Th cells, which are considered useful for monitoring the establishment of acquired immunity after vaccination.
Sequence Data -
Mutation Information
Note
Basic Characteristics of Mutations
  • Mutation Site: The specific location in a gene or protein sequence where a change occurs.
  • Mutation Level: The level at which a mutation occurs, including the nucleotide or amino acid level.
  • Mutation Type: The nature of the mutation, such as missense mutation, nonsense mutation, synonymous mutation, etc.
  • Gene/Protein/Region: Refers to the specific region of the virus where the mutation occurs. Including viral genes, viral proteins, or a specific viral genome region. If the article does not specifically indicate the relationship between the mutation and its correspondence, the main
  • Gene/Protein/Region studied in the article is marked.
  • Genotype/Subtype: Refers to the viral genotype or subtype where the mutation occurs. If the article does not specifically indicate the relationship between the mutation and its correspondence, the main Genotype/Subtype studied in the article is marked.
  • Viral Reference: Refers to the standard virus strain used to compare and analyze viral sequences.
Functional Impact and Mechanisms
  • Disease: An abnormal physiological state with specific symptoms and signs caused by viral infection.
  • Immune: The article focuses on the study of mutations and immune.
  • Target Gene: Host genes that viral mutations may affect.
Clinical and Epidemiological Correlations
  • Clinical Information: The study is a clinical or epidemiological study and provides basic information about the population.
  • Treatment: The study mentioned a certain treatment method, such as drug resistance caused by mutations. If the study does not specifically indicate the relationship between mutations and their correspondence treatment, the main treatment studied in the article is marked.
  • Location: The source of the research data.
Literature Information
  • Sequence Data: The study provides the data accession number.