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结核分枝杆菌菌株抗原 Rv2945c 和 Rv0309 的遗传多样性可能反映了持续的免疫逃避。

Genetic diversity of antigens Rv2945c and Rv0309 in Mycobacterium tuberculosis strains may reflect ongoing immune evasion.

机构信息

National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention/State Key Laboratory for Infectious Disease Prevention and Control, Beijing, China; Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou, China.

出版信息

FEMS Microbiol Lett. 2013 Oct;347(1):77-82. doi: 10.1111/1574-6968.12222. Epub 2013 Aug 23.

DOI:10.1111/1574-6968.12222
PMID:23889607
Abstract

Host immune pressure and associated immune evasion of pathogenic bacteria are key features of host-pathogen co-evolution. A previous study showed that human T-cell epitopes of Mycobacterium tuberculosis are evolutionarily hyperconserved and thus it was deduced that M. tuberculosis lacks antigenic variation and immune evasion. Here, we selected 173 clinical M. tuberculosis complex (MTBC) isolates from China, amplified the genes encoding Rv2945c and Rv0309, and compared the sequences. The results showed that genetic diversity existed in these two genes among the MTBC strains and two single nucleotide polymorphisms (SNPs) presented higher polymorphisms. Antigen Rv2945c harbored a higher number of amino acid substitutions of its T-cell epitopes, which may reflect ongoing immune evasion. In addition, the high dN/dS value of Rv0309 suggested antigen Rv0309 might be involved in diversifying selection to evade host immunity. Finally, a small group of strains were identified based on the genetic diversity of these two genes, which might indicate that they interact differently with human T cells compared with other strains.

摘要

宿主免疫压力和相关的致病细菌免疫逃逸是宿主-病原体共同进化的关键特征。先前的研究表明,结核分枝杆菌的人类 T 细胞表位是进化上高度保守的,因此可以推断结核分枝杆菌缺乏抗原变异和免疫逃逸。在这里,我们从中国选择了 173 株临床结核分枝杆菌复合群(MTBC)分离株,扩增了编码 Rv2945c 和 Rv0309 的基因,并比较了这些基因的序列。结果表明,这两个基因在 MTBC 菌株中存在遗传多样性,并且有两个单核苷酸多态性(SNP)表现出较高的多态性。抗原 Rv2945c 其 T 细胞表位的氨基酸替换数量较高,这可能反映了持续的免疫逃逸。此外,Rv0309 的高 dN/dS 值表明抗原 Rv0309 可能参与了多样化选择以逃避宿主免疫。最后,根据这两个基因的遗传多样性,确定了一小部分菌株,这可能表明它们与人类 T 细胞的相互作用与其他菌株不同。

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