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Analysis of molecular escape mechanism of Theileria

泰勒虫分子逃逸机制分析

基本信息

批准号：
05454115
负责人：
ONUMA Misao
金额：
$ 4.22万
依托单位：
Hokkaido University
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (B)
财政年份：
1993
资助国家：
日本
起止时间：
1993 至 1994
项目状态：
已结题

项目摘要

Cattle in Japan have been found to be infected with Theileria sergenti. Antigenic polymorphism has been demonstrated among stocks or field isolates of T.sergenti by using monoclonal antibodies. The results of Southern blot hybridization have also shown the genomic diversity of T.sergenti isolates.As one of the mechanisms that the parasitic protozoa evade host immune responses, they are known to express surface molecules with variant antigenic forms. This antigenic variation is related to change at genomic level, point mutatation, deletion or gene rearrangement in malaria and trypanosomes.To understand the evasion mechanism of T.sergenti, we analyzed one of the major surface proteins of merozoites (p32). We isolated 3 clones from cDNA library and nucleotide sequences were determined. Comparison of nucleotide sequences reveals at least 3 genetically different parasite population may coexist, and that transition of predominant parasite populations might occur during persistent infection. We further analyzed p32 antigenic difference of parasites obtained from different parasitemia peaks. Antigenic differences were observed among parasites from different peaks during persistent infection.There is a good correlation between the genotype changes and antibody responses. Population change in vivo indicates one of the parasite evasion mechanisms from host immune responses, because genetically different population may express antigenically different surface molecules.

日本的牛被发现感染了瑟氏杆菌。利用单克隆抗体的方法证实了血清绦虫种群或野外分离株的抗原多态性。Southern blot杂交结果也显示了分离菌株的基因组多样性。作为寄生原生动物逃避宿主免疫应答的机制之一，它们表达具有不同抗原形式的表面分子。在疟疾和锥虫中，这种抗原变异与基因组水平的变化、点突变、缺失或基因重排有关。为了了解梭形菌的逃逸机制，我们分析了一种主要的分裂子表面蛋白（p32）。从cDNA文库中分离3个克隆，测定核苷酸序列。核苷酸序列比较表明，至少3个遗传上不同的寄生虫种群可能共存，并且在持续感染期间可能发生优势寄生虫种群的转变。我们进一步分析了不同寄生峰获得的寄生虫的p32抗原差异。在持续感染期间，不同高峰的寄生虫之间存在抗原差异。基因型变化与抗体反应之间存在良好的相关性。体内种群变化提示了寄生虫逃避宿主免疫反应的机制之一，因为遗传上不同的种群可能表达不同的抗原表面分子。