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免疫信息学预测人类冠状病毒的潜在免疫优势表位及其与自身免疫的关联。

Immunoinformatics prediction of potential immunodominant epitopes from human coronaviruses and association with autoimmunity.

机构信息

Biomedical Research Center, Qatar University, 2713, Doha, Qatar.

Research and Development Department, Barzan Holdings, 7178, Doha, Qatar.

出版信息

Immunogenetics. 2022 Apr;74(2):213-229. doi: 10.1007/s00251-021-01250-5. Epub 2022 Jan 10.

Abstract

Cross-reactivity between different human coronaviruses (HCoVs) might contribute to COVID-19 outcomes. Here, we aimed to predict conserved peptides among different HCoVs that could elicit cross-reacting B cell and T cell responses. Three hundred fifty-one full-genome sequences of HCoVs, including SARS-CoV-2 (51), SARS-CoV-1 (50), MERS-CoV (50), and common cold species OC43 (50), NL63 (50), 229E (50), and HKU1 (50) were downloaded aligned using Geneious Prime 20.20. Identification of epitopes in the conserved regions of HCoVs was carried out using the Immune Epitope Database (IEDB) to predict B- and T-cell epitopes. Further, we identified sequences that bind multiple common MHC and modeled the three-dimensional structures of the protein regions. The search yielded 73 linear and 35 discontinuous epitopes. A total of 16 B-cell and 19 T-cell epitopes were predicted through a comprehensive bioinformatic screening of conserved regions derived from HCoVs. The 16 potentially cross-reactive B-cell epitopes included 12 human proteins and four viral proteins among the linear epitopes. Likewise, we identified 19 potentially cross-reactive T-cell epitopes covering viral proteins. Interestingly, two conserved regions: LSFVSLAICFVIEQF (NSP2) and VVHSVNSLVSSMEVQSL (spike), contained several matches that were described epitopes for SARS-CoV. Most of the predicted B cells were buried within the SARS-CoV-2 protein regions' functional domains, whereas T-cell stretched close to the functional domains. Additionally, most SARS-CoV-2 predicted peptides (80%) bound to different HLA types associated with autoimmune diseases. We identified a set of potential B cell and T cell epitopes derived from the HCoVs that could contribute to different diseases manifestation, including autoimmune disorders.

摘要

不同的人类冠状病毒 (HCoV) 之间的交叉反应可能导致 COVID-19 的发生。在这里,我们旨在预测不同 HCoV 之间可能引起交叉反应的 B 细胞和 T 细胞反应的保守肽。我们下载了包括 SARS-CoV-2(51 个)、SARS-CoV-1(50 个)、MERS-CoV(50 个)和普通感冒种 OC43(50 个)、NL63(50 个)、229E(50 个)和 HKU1(50 个)在内的 351 个完整基因组序列,并使用 Geneious Prime 20.20 进行了对齐。使用免疫表位数据库(IEDB)对 HCoV 保守区域中的表位进行鉴定,以预测 B 细胞和 T 细胞表位。此外,我们鉴定了与多种常见 MHC 结合的序列,并对蛋白质区域的三维结构进行建模。搜索结果产生了 73 个线性和 35 个不连续的表位。通过对源自 HCoV 的保守区域进行全面的生物信息学筛选,共预测了 16 个 B 细胞和 19 个 T 细胞表位。在这 16 个潜在的交叉反应性 B 细胞表位中,有 12 个人类蛋白和 4 个病毒蛋白属于线性表位。同样,我们鉴定了 19 个潜在的交叉反应性 T 细胞表位,涵盖了病毒蛋白。有趣的是,两个保守区域:LSFVSLAICFVIEQF(NSP2)和 VVHSVNSLVSSMEVQSL(spike),包含了几个被描述为 SARS-CoV 表位的匹配物。大多数预测的 B 细胞都位于 SARS-CoV-2 蛋白区域的功能域内,而 T 细胞则靠近功能域伸展。此外,大多数 SARS-CoV-2 预测的肽(80%)与自身免疫性疾病相关的不同 HLA 类型结合。我们鉴定了一组源自 HCoV 的潜在 B 细胞和 T 细胞表位,这些表位可能导致包括自身免疫性疾病在内的不同疾病的表现。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c6fe/8744044/b8b2e8fe6604/251_2021_1250_Fig1_HTML.jpg

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