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利用计算机预测 PmpD 中的 T 细胞和 B 细胞表位:设计沙眼衣原体疫苗的第一步。

In silico prediction of T- and B-cell epitopes in PmpD: First step towards to the design of a Chlamydia trachomatis vaccine.

机构信息

Basic Immunology Laboratory, Faculty of Biochemistry and Biological Sciences, National University of the Littoral, Santa Fe, Argentina.

Independent professional, C1425BME, Buenos Aires, Argentina.

出版信息

Biomed J. 2018 Apr;41(2):109-117. doi: 10.1016/j.bj.2018.04.007. Epub 2018 May 21.

Abstract

BACKGROUND

Chlamydia trachomatis is the most common sexually transmitted bacterial infection globally. Currently, there are no vaccines available despite the efforts made to develop a protective one. Polymorphic membrane protein D (PmpD) is an attractive immunogen candidate as it is conserved among strains and it is target of neutralizing antibodies. However, its high molecular weight and its complex structure make it difficult to handle by recombinant DNA techniques. Our aim is to predict B-cell and T-cell epitopes of PmpD.

METHOD

A sequence (Genbank AAK69391.2) having 99-100% identity with various serovars of C. trachomatis was used for predictions. NetMHC and NetMHCII were used for T-cell epitope linked to MHC I or MHC II alleles prediction, respectively. BepiPred predicted linear B-cell epitopes. For three dimensional epitopes, PmpD was homology-modeled by Raptor X. Surface epitopes were predicted on its globular structure using DiscoTope.

RESULTS

NetMHC predicted 271 T-cell epitopes of 9-12aa with weak affinity, and 70 with strong affinity to MHC I molecules. NetMHCII predicted 2903 T-cell epitopes of 15aa with weak affinity, and 742 with strong affinity to MHC II molecules. Twenty four linear B-cell epitopes were predicted. Raptor X was able to model 91% of the three-dimensional structure whereas 57 residues of discontinuous epitopes were suggested by DiscoTope. Six regions containing B-cell and T-cell epitopes were identified by at least two predictors.

CONCLUSIONS

PmpD has potential B-cell and T-cell epitopes distributed throughout the sequence. Thus, several fragments were identified as valuable candidates for subunit vaccines against C. trachomatis.

摘要

背景

沙眼衣原体是全球最常见的性传播细菌感染。尽管已经做出了开发保护性疫苗的努力,但目前仍没有可用的疫苗。多态膜蛋白 D (PmpD) 是一种有吸引力的免疫原候选物,因为它在菌株之间保守,并且是中和抗体的靶标。然而,由于其分子量高且结构复杂,因此难以通过重组 DNA 技术进行处理。我们的目标是预测 PmpD 的 B 细胞和 T 细胞表位。

方法

使用与各种沙眼衣原体血清型具有 99-100%同一性的序列(Genbank AAK69391.2)进行预测。NetMHC 和 NetMHCII 分别用于预测与 MHC I 或 MHC II 等位基因相关的 T 细胞表位。BepiPred 预测线性 B 细胞表位。对于三维表位,使用 Raptor X 对 PmpD 进行同源建模。使用 DiscoTope 在其球状结构上预测表面表位。

结果

NetMHC 预测了 271 个 9-12aa 的 T 细胞表位,亲和力较弱,70 个亲和力较强的表位与 MHC I 分子结合。NetMHCII 预测了 2903 个 15aa 的 T 细胞表位,亲和力较弱,742 个亲和力较强的表位与 MHC II 分子结合。预测了 24 个线性 B 细胞表位。Raptor X 能够对三维结构的 91%进行建模,而 DiscoTope 则建议了 57 个不连续表位的残基。至少有两个预测器识别出包含 B 细胞和 T 细胞表位的六个区域。

结论

PmpD 具有分布在整个序列中的潜在 B 细胞和 T 细胞表位。因此,已经鉴定出几个片段作为针对沙眼衣原体的亚单位疫苗的有价值候选物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/11b2/6138762/eab391f60902/gr1.jpg

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