Zamanzadeh Zahra, Ataei Mitra, Nabavi Seyed Massood, Ahangari Ghasem, Sadeghi Mehdi, Sanati Mohammad Hosein
Department of medical biotechnology. Institute of Medical Genetic, National Institute of Genetics Engineering and Biotechnology (NIGEB), Tehran, 14965/161 Iran.
Department of Neurology, Faculty of Public Health, Shahed University, Tehran, 18155/159, Iran.
Iran J Biotechnol. 2017 Mar;15(1):10-21. doi: 10.15171/ijb.1356.
Multiple sclerosis (MS) is the most common autoimmune disease of the central nervous system (CNS). The main cause of the MS is yet to be revealed, but the most probable theory is based on the molecular mimicry that concludes some infections in the activation of T cells against brain auto-antigens that initiate the disease cascade.
The Purpose of this research is the prediction of the auto-antigen potency of the myelin proteolipid protein (PLP) in multiple sclerosis.
As there wasn't any tertiary structure of PLP available in the Protein Data Bank (PDB) and in order to characterize the structural properties of the protein, we modeled this protein using prediction servers. Meta prediction method, as a new perspective , was performed to fi nd PLPs epitopes. For this purpose, several T cell epitope prediction web servers were used to predict PLPs epitopes against Human Leukocyte Antigens (HLA). The overlap regions, as were predicted by most web servers were selected as immunogenic epitopes and were subjected to the BLASTP against microorganisms.
Three common regions, AA, AA, and AA were detected as immunodominant regions through meta-prediction. Investigating peptides with more than 50% similarity to that of candidate epitope AA in bacteria showed a similar peptide in bacteria (mainly consistent with that of clostridium and mycobacterium) and spike protein of Alphacoronavirus 1, Canine coronavirus, and Feline coronavirus. These results suggest that cross reaction of the immune system to PLP may have originated from a bacteria or viral infection, and therefore molecular mimicry might have an important role in the progression of MS.
Through reliable and accurate prediction of the consensus epitopes, it is not necessary to synthesize all PLP fragments and examine their immunogenicity experimentally (). In this study, the best encephalitogenic antigens were predicted based on bioinformatics tools that may provide reliable results for researches in a shorter time and at a lower cost.
多发性硬化症(MS)是中枢神经系统(CNS)最常见的自身免疫性疾病。MS的主要病因尚未明确,但最有可能的理论基于分子模拟,即某些感染在激活针对脑自身抗原的T细胞过程中引发了疾病级联反应。
本研究旨在预测髓鞘蛋白脂蛋白(PLP)在多发性硬化症中的自身抗原效力。
由于蛋白质数据库(PDB)中没有PLP的三级结构,为了表征该蛋白质的结构特性,我们使用预测服务器对其进行建模。采用元预测方法作为一种新视角来寻找PLP的表位。为此,使用了多个T细胞表位预测网络服务器来预测PLP针对人类白细胞抗原(HLA)的表位。将大多数网络服务器预测的重叠区域选为免疫原性表位,并对微生物进行BLASTP分析。
通过元预测检测到三个共同区域,即AA、AA和AA为免疫显性区域。对与候选表位AA相似度超过50%的细菌肽段进行研究发现,细菌中存在一种相似肽段(主要与梭菌和分枝杆菌一致)以及甲型冠状病毒1、犬冠状病毒和猫冠状病毒的刺突蛋白。这些结果表明,免疫系统对PLP的交叉反应可能源于细菌或病毒感染,因此分子模拟可能在MS的进展中起重要作用。
通过对共有表位进行可靠且准确的预测,无需合成所有PLP片段并通过实验检测其免疫原性()。在本研究中,基于生物信息学工具预测出了最佳致脑炎性抗原,这可能在更短时间内以更低成本为研究提供可靠结果。