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[参与10种不同物种间交叉反应的新型原肌球蛋白共有B和T表位。一项计算机模拟研究]

[Novel tropomyosin consensus B and T epitopes involved in cross-reactivity between 10 different species. An in silico study].

作者信息

Fang Luis, Martínez Dalgys, Meza-Torres Catherine, Moreno-Woo Ana, Pereira-Sanandrés Nicole, Vargas Alex Domínguez, Garavito Gloria, Egea Eduardo

机构信息

Universidad del Norte. División Ciencias de la Salud, Departamento de Medicina. Barranquilla, Colombia.

Universidad de Cartagena. Instituto de Investigaciones Inmunológicas. Cartagena, Colombia.

出版信息

Rev Alerg Mex. 2024 Feb 1;71(1):60. doi: 10.29262/ram.v71i1.1367.

DOI:10.29262/ram.v71i1.1367
PMID:38683078
Abstract

OBJECTIVE

This study aimed to identify by in silico methods tropomyosin consensus B and T epitopes of shrimp species, house dust mites, insects, and nematodes associated with allergic diseases in tropical countries.

METHODS

In silico analysis included tropomyosin from mites (Der p 10, Der f 10, Blo t 10), insects (Aed a 10, Per a 7, Bla g 7), shrimp (Lit v 1, Pen m 1, Pen a 1), and nematode (Asc l 3) all sequences were taken from the UniProt database. Linear IgE epitopes were predicted with AlgPred 2.0 and validated with BepiPred 3.0. MHC-II binding T cell epitopes were predicted using the IEDB server, which implements nine predictive methods (consensus method, combinatorial library, NN-align-2.3, NN- align-2.2, SMM-align, Sturniolo, NetMHCIIpan 3.1, and NetMHCIIpan 3.2) these predictions focused on 10 HLA-DR and 2 HLA-DQ alleles associated with allergic diseases. Subsequently, consensus B and T epitopes present in all species were identified.

RESULTS

We identified 12 sequences that behaved as IgE-epitopes and B-cell epitopes, three of them: 160RKYDEVARKLAMVEA174, 192ELEEELRVVGNNLKSLEVSEEKAN215, 251KEVDRLEDELV261 were consensus in all species. Eleven peptides (T-epitopes) showed strong binding (percentile rank ≤ 2.0) to HLA-DRB1*0301, *0402, 0411, 0701, 1101, 1401, HLA-DQA103:01/DQB103:02, and HLA- DQA105:01/DQB102:01. Only two T-epitopes were consensus in all species: 167RKLAMVEADLERAEERAEt GEsKIVELEEELRV199, and 218EEeY KQQIKT LTaKLKEAEARAEFAERSV246. Subsequently, we identified 2 B and T epitope sequences and reached a consensus between species 167RKLAMVEA174 and 192ELEEELRV199.

CONCLUSIONS

These data describe three sequences that may explain the IgE cross-reactivity between the analyzed species. In addition, the consensus B and T epitopes can be used for further in vitro investigations and may help to design multiple-epitope protein-based immunotherapy for tropomyosin-related allergic diseases.

摘要

目的

本研究旨在通过计算机模拟方法鉴定与热带国家过敏性疾病相关的虾类、屋尘螨、昆虫和线虫的原肌球蛋白共有B和T表位。

方法

计算机模拟分析包括来自螨类(Der p 10、Der f 10、Blo t 10)、昆虫(Aed a 10、Per a 7、Bla g 7)、虾类(Lit v 1、Pen m 1、Pen a 1)和线虫(Asc l 3)的原肌球蛋白,所有序列均取自UniProt数据库。使用AlgPred 2.0预测线性IgE表位,并用BepiPred 3.0进行验证。使用实施九种预测方法(共有方法、组合文库、NN-align-2.3、NN-align-2.2、SMM-align、Sturniolo、NetMHCIIpan 3.1和NetMHCIIpan 3.2)的IEDB服务器预测MHC-II结合T细胞表位,这些预测集中于与过敏性疾病相关的10个HLA-DR和2个HLA-DQ等位基因。随后,鉴定出所有物种中存在的共有B和T表位。

结果

我们鉴定出12个表现为IgE表位和B细胞表位的序列,其中3个:160RKYDEVARKLAMVEA174、192ELEEELRVVGNNLKSLEVSEEKAN215、251KEVDRLEDELV261在所有物种中是共有的。11种肽(T表位)对HLA-DRB1*0301、*0402、0411、0701、1101、1401、HLA-DQA103:01/DQB103:02和HLA-DQA105:01/DQB102:01表现出强烈结合(百分位数排名≤2.0)。只有2个T表位在所有物种中是共有的:167RKLAMVEADLERAEERAEt GEsKIVELEEELRV199和218EEeY KQQIKT LTaKLKEAEARAEFAERSV246。随后,我们鉴定出2个B和T表位序列,并在物种167RKLAMVEA174和192ELEEELRV199之间达成共识。

结论

这些数据描述了三个可能解释所分析物种之间IgE交叉反应性的序列。此外,共有B和T表位可用于进一步的体外研究,并可能有助于设计针对原肌球蛋白相关过敏性疾病的基于多表位蛋白的免疫疗法。

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