Impact of mutations in immunodominant regions of SARS-CoV-2 variants on recognition by CD8+ T cell: An in silico analysis.

Publication date: Aug 01, 2025

This study aimed to investigate whether mutations in the immunodominant regions of the S, M, and N proteins of the Gamma, Delta, and Omicron SARS-CoV-2 variants that circulated in Brazil affect the recognition of viral antigens by Brazilian HLA-I-restricted CD8+ T cell epitopes, using an in silico approach. Sequences of the Gamma (n = 36,174), Delta (n = 35,129), and Omicron (n = 336) variants were retrieved using GISAID. Consensus sequences were generated using Geneious software with NC045512 as a reference. Epitopes for the S, M, and N proteins of both the original and variant sequences were predicted using NetCTLpan 1. 1, NetMHCpan 4. 0, and VaxiJen v2. 0. The positions occupied by these epitopes, with high probability of presentation, affinity to HLA molecules, and antigenicity, were identified as potentially immunodominant regions. The S protein of the reference sequence (NC045512) and its variants contained 17 immunodominant regions. Delta showed the highest conservation (94. 1 %, 16), followed by Gamma (82. 3 %, 14) and Omicron (70. 5 %, 12). Omicron exhibited the greatest mutational variability and had regions of increased antigenicity and two novel immunodominant regions with broader human leukocyte antigen (HLA) recognition. Additionally, Omicron lost two previously identified immunodominant regions and had one region of reduced antigenicity that did not affect HLA recognition. Gamma had mutations in three regions that increased both antigenicity and HLA recognition. Delta had only one mutated region with lower antigenicity, which did not affect HLA recognition. Notably, new immunodominant regions for the M and N proteins appeared in the Omicron variant. Brazilian HLA-I-restricted CD8+ T cell epitopes from SARS-CoV-2 immunodominant regions are partially conserved in the Gamma, Delta, and Omicron variants circulating in Brazil, suggesting effective a cross-protective immune response that may help reduce COVID-19 severity and mortality.

Concepts Keywords
Antigenicity Brazil
Brazil CD8 T epitopes
Mortality CD8-Positive T-Lymphocytes
Nc045512 Computational analysis
Viral Computer Simulation
Coronavirus M Proteins
Coronavirus M Proteins
Coronavirus Nucleocapsid Proteins
Coronavirus Nucleocapsid Proteins
COVID-19
Epitopes, T-Lymphocyte
Epitopes, T-Lymphocyte
Humans
Immunodominant Epitopes
Immunodominant Epitopes
Immunodominant region
In silico
Mutation
SARS-CoV-2
SARS-CoV-2
Spike Glycoprotein, Coronavirus
Spike Glycoprotein, Coronavirus
spike protein, SARS-CoV-2
Variants of concern

Semantics

Type Source Name
disease IDO cell
disease IDO immune response
disease MESH COVID-19

Original Article

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