减弱但具有免疫刺激性的Mycobacterium结核病变体bovis菌株Ravenel显示T细胞表位的变化
Evan P Brenner1, Srinand Sreevatsan2
1Department of Pathobiology and Diagnostic Investigation, College of Veterinary Medicine, Michigan State University, 784 Wilson Road, East Lansing, MI, 48824, USA.
Scientific reports
|July 31, 2023
概括
结核菌菌菌的结核病变种. 波维斯 (MBO) 菌株Ravenel表现出改变的T细胞表位,这可能解释了与毒性菌株相比,其减弱的致病性. 这些变异为MBO毒性和潜在的疫苗标提供了洞察力.
科学领域:
- 兽医微生物学 兽医微生物学
- 免疫学 免疫学 免疫学
- 基因组学就是基因组学.
背景情况:
- 结核病 (TB) 在全球范围内影响人类和动物,由Mycobacterium结核病综合体 (MTBC) 引起.
- MTBC通过抗原呈现来操纵宿主免疫力;表位序列通常是超保存的.
- 结核菌菌菌的结核病变种. bovis (MBO) 菌株 拉维内尔在牛中引起强烈的免疫反应,但显示出有缺陷的致病性.
研究的目的:
- 通过使用全基因组测序来研究MBO菌株Ravenel的表位序列变异.
- 为了比较这些变异与完全有毒的MBO临床分离物 (菌株10-7428).
- 评估已识别的表位变异对MBO病原和减弱的潜在影响.
主要方法:
- 整体基因组测序的MBO菌株拉文尔.
- 将4818个验证的MTBC表位与MBO Ravenel和MBO 10-7428中的序列进行比较.
- 生物信息分析用于预测表位组修饰对蛋白质稳定性的影响.
主要成果:
- MBO菌株Ravenel在基因rpfB,argC和rpoA中表现出3种修饰的T细胞表位.
- 预计这些修改对蛋白质稳定性的影响最小.
- 毒性MBO菌株10-7428中的所有T细胞表位都是野生型 (WT).
结论:
- 在MBO Ravenel中改变的T细胞表位支持它们在应变减弱中的作用.
- 鉴定到的基因变异可能为MBO的病原体提供了洞察力.
- 这些基因代表了反向疫苗学方法的潜在目标.
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