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与布氏锥虫抗原变异相关的基因组重排。

Genomic rearrangements correlated with antigenic variation in Trypanosoma brucei.

作者信息

Williams R O, Young J R, Majiwa P A

出版信息

Nature. 1979;282(5741):847-9. doi: 10.1038/282847a0.

Abstract

The capacity of African trypanosomes to express sequentially a large repertoire of different surface antigens during an infection enables the parasite to evade the immune response of its host, and makes attempts to produce a vaccine against the disease difficult. It is evident that point mutations cannot account for antigen diversity. Variable antigens like immunoglobulins are derived from an extensive family of genes of which only one is expressed in a given cell. As somatic tic recombination is involved in the immunoglobulin gene system, this similarity prompted us to search for somatic rearrangements in trypanosome variable antigen genes. We have constructed a recombinant plasmid containing approximately half the DNA sequence coding for a Trypanosoma brucei variable antigen and hybridised the inserted sequences to various restriction enzyme digests of nuclear DNA from different trypanosome clones. Differences in the sizes of restriction tion fragments hybridising to the inserted variable antigen coding sequence show altered positions of enzyme sites relative to this sequence, indicating different arrangements of DNA sequences around this gene in different trypanosome clones.

摘要

非洲锥虫在感染过程中依次表达大量不同表面抗原的能力,使该寄生虫能够逃避宿主的免疫反应,并使得研制针对该疾病的疫苗变得困难。显然,点突变无法解释抗原多样性。像免疫球蛋白一样的可变抗原源自一个庞大的基因家族,在给定细胞中只有一个基因会表达。由于体细胞重排参与免疫球蛋白基因系统,这种相似性促使我们在锥虫可变抗原基因中寻找体细胞重排。我们构建了一个重组质粒,其包含编码布氏锥虫可变抗原约一半的DNA序列,并将插入序列与来自不同锥虫克隆的核DNA的各种限制性酶切片段杂交。与插入的可变抗原编码序列杂交的限制性片段大小不同,表明酶切位点相对于该序列的位置发生了改变,这表明在不同锥虫克隆中该基因周围的DNA序列排列不同。

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