新型冠状病毒变异株免疫显性区域突变对CD8 + T细胞识别的影响：一项计算机模拟分析。
Impact of mutations in immunodominant regions of SARS-CoV-2 variants on recognition by CD8+ T cell: An in silico analysis.
作者信息
da Silva Greice Carolina Santos, Paraná Victoria Cruz, de Almeida Rego Filipe Ferreira, Portela Mariana Maciel, Queiroz Mariana Barros, Junior Raimundo Coutinho, da Silva Carlos Gustavo Regis, Gois Luana Leandro, Grassi Maria Fernanda Rios
机构信息
Fundação Oswaldo Cruz, Instituto Gonçalo Moniz, Laboratório Avançado de Saúde Pública, Salvador, Bahia, Brazil.
Fundação Oswaldo Cruz, Instituto Gonçalo Moniz, Laboratório Avançado de Saúde Pública, Salvador, Bahia, Brazil; Escola Bahiana de Medicina e Saúde Pública, Salvador, Bahia, Brazil.
出版信息
J Infect Public Health. 2025 Aug;18(8):102803. doi: 10.1016/j.jiph.2025.102803. Epub 2025 May 3.
BACKGROUND
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.
METHODS
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.
RESULTS
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.
CONCLUSIONS
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.
背景
本研究旨在利用计算机模拟方法，调查在巴西流行的新冠病毒伽马、德尔塔和奥密克戎变异株的刺突蛋白（S）、膜蛋白（M）和核衣壳蛋白（N）免疫显性区域的突变，是否会影响巴西人HLA-I类分子限制性CD8+T细胞表位对病毒抗原的识别。
方法
利用全球共享流感数据倡议组织（GISAID）获取伽马变异株（n = 36174）、德尔塔变异株（n = 35129）和奥密克戎变异株（n = 336）的序列。以NC045512为参考序列，使用Geneious软件生成共识序列。利用NetCTLpan 1.1、NetMHCpan 4.0和VaxiJen v2.0预测原始序列和变异序列的S、M和N蛋白的表位。这些表位占据的位置，具有高概率的呈递、对HLA分子的亲和力和抗原性，被确定为潜在的免疫显性区域。
结果
参考序列（NC045512）及其变异株的S蛋白包含17个免疫显性区域。德尔塔变异株的保守性最高（94.1%，16个），其次是伽马变异株（82.3%，14个）和奥密克戎变异株（70.5%，12个）。奥密克戎变异株表现出最大的突变变异性，有抗原性增加的区域和两个新的免疫显性区域，具有更广泛的人类白细胞抗原（HLA）识别。此外，奥密克戎变异株失去了两个先前确定的免疫显性区域，有一个抗原性降低的区域，但不影响HLA识别。伽马变异株在三个区域发生突变，增加了抗原性和HLA识别。德尔塔变异株只有一个抗原性较低的突变区域，不影响HLA识别。值得注意的是，奥密克戎变异株出现了M和N蛋白的新免疫显性区域。
结论
来自新冠病毒免疫显性区域巴西人HLA-I类分子限制性CD8+T细胞表位在巴西流行的伽马、德尔塔和奥密克戎变异株中部分保守，提示可能存在有效的交叉保护性免疫反应，有助于降低新冠的严重程度和死亡率。
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