结核分枝杆菌抗原PE35和PPE68基因多态性的初步研究

发布时间：2018-10-19 19:27

【摘要】：目的为研究结核分枝杆菌RD1区编码PE/PPE蛋白家族中的PE 35和PPE 68基因的多态性,并评估其基因多态性对免疫识别的影响。方法笔者从本实验室保存的来自国内不同地区的2346株结核分枝杆菌复合群临床分离株中,选取代表不同Spoligotyping类型的161株临床分离结核分枝杆菌菌株,基因扩增后进行序列比对,比较其在T细胞抗原表位的差异。结果在161株菌株中,23株显示有PE 35基因多态性,8株有PPE 68基因多态性。在PE 35基因中,除了菌株JL06018的突变外的其余突变都导致其T细胞抗原表位的改变。PPE 68基因中,62个T细胞表位中有58个(占93.5%)发生了改变。非北京家族PE 35基因的突变率明显高于北京家族(P0.05),而PPE 68基因突变虽是非北京家族高于北京家族,但差异无统计学意义。结论 PE 35和PPE 68的编码基因存在明显的多态性,并很有可能导致蛋白功能的明显改变。此外,这2个蛋白的人类T细胞表位是高度可变的,提示这2种蛋白可能通过参与分化选择来逃避宿主免疫。北京家族可能比非北京家族更容易被宿主T细胞识别,进而更容易传播。
[Abstract]:Objective to study the polymorphism of PE 35 and PPE 68 genes in the PE/PPE protein family of Mycobacterium tuberculosis RD1 region and to evaluate the effect of the polymorphism on immune recognition. Methods from 2346 strains of Mycobacterium tuberculosis complex isolated from different regions in our laboratory, 161 clinical isolates representing different Spoligotyping types were selected and sequenced after gene amplification. The differences in T cell epitopes were compared. Results among 161 strains, 23 showed polymorphism of PE 35 gene and 8 showed polymorphism of PPE 68 gene. In the PE 35 gene, all the mutations except the mutation of strain JL06018 resulted in the alteration of T cell epitope. 58 (93.5%) of 62 T cell epitopes of the PPE 68 gene were changed. The mutation rate of PE 35 gene in non-Beijing family was significantly higher than that in Beijing family (P0.05), while the mutation rate of PPE 68 gene was higher in non-Beijing family than in Beijing family, but the difference was not statistically significant. Conclusion there are significant polymorphisms in the coding genes of PE 35 and PPE 68, which may lead to obvious changes in protein function. In addition, the human T cell epitopes of these two proteins are highly variable, suggesting that these two proteins may be involved in the selection of differentiation to avoid host immunity. Beijing families may be more easily identified by host T cells than non-Beijing families, and thus more easily transmitted.
【作者单位】：中国疾病预防控制中心传染病预防控制所传染病预防控制国家重点实验室;感染性疾病诊治协同创新中心;
【基金】：国家自然科学基金(No.81401647) 国家科技重大专项(No.2013ZX10003006,2013ZX10003002-001)~~
【分类号】：R378.911

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