MECHANISMS OF ANTIGENIC DIVERSITY IN TRYPANOSOMA BRUCEI

锥虫病是人类和牲畜发展的严重制约因素 在非洲的许多地方。 对寄生虫免疫的发展是 由于抗原变异，由于a 表面糖蛋白（可变表面糖蛋白或VSG）。 的基因 用于VSG的编码可以迅速发展。 因此，特定的VSG基因可能 在许多不同的股票或只有几个代表。 此外，VSG 基因可以在每个股票中以相同的拷贝存在，或者以部分拷贝存在。 同源基因拷贝。 产生生物多样性的分子机制 VSG基因库尚不清楚，尽管已有证据表明， 获得基因转换和点突变。 锥虫有 从相同的血清群中分离出来，这些血清群共享可变数量的 暴露的表面表位。 这些锥虫中表达的VSG基因 可能是进化基因的例子，这些基因的序列关系与 祖先生物体仍然很明显。 VSG基因的结构 将祖先生物体和相关后代中的生物体与 提出了VSG基因进化的机制，以及锥虫 继续向宿主免疫系统提供新的表位。 该方法将涉及VSG基因的克隆和来自祖细胞的cDNA 锥虫和血清学后代。 克隆的DNA 通过限制性内切酶和S1核酸酶图谱比较。 具体目标 为： (a)从一个布氏锥虫克隆种群中分离出5个克隆种群， 共享暴露的表面表位的血清群; (b)以确定是否有基因的完整基本拷贝 五种相关VSG中的每一种的表达预先存在于祖细胞中， 有机体;以及 (c)如果在祖生物体中不存在完整的基本拷贝， 定义表达的VSG基因产生的机制。 锥虫表面抗原多样性的机制可能是广泛的 在其他持续性传染病中的意义， 持久性的基础并没有很好的定义。

Trypanosomiasis is a severe constraint to human and livestock development in many parts of Africa. Development of immunity to the parasite is ineffective because of antigenic variation, due to changes in sequence of a surface glycoprotein (the variable surface glycoprotein or VSG). The genes coding for VSGs can evolve rapidly. Therefore, a particular VSG gene may be represented in many different stocks or in only a few. Also, the VSG gene may exist as an identical copy in each stock or as a partially homologous gene copy. The molecular mechanisms generating diversity in the VSG gene repertoire are not clearly understood, although evidence has been obtained for both gene conversion and point mutation. Trypanosomes have been isolated from the same serodeme which share variable numbers of exposed, surface epitopes. The expressed VSG genes in these trypanosomes may be examples of evolving genes whose sequence relationship to genes in the progenitor organism is still apparent. The structure of VSG genes in the progenitor organism and in the related progeny will be compared to suggest mechanisms by which VSG genes evolve, and by which the trypanosome continues to present new epitopes to the host immune system. The methodology will involve cloning of VSG genes and cDNAs from progenitor trypanosome and the serologically progeny. The cloned DNAs will be compared by restriction enzyme and S1 nuclease mapping. The specific aims are: (a) to isolate five cloned populations of Trypanosoma brucei from one serodeme which share exposed surface epitopes; (b) to determine whether complete basic copies of the genes responseble for expression of each of the five related VSGs pre-exist in the progenitor organism; and (c) where complete basic copies do not exist in the progenitor organism, to define the mechanisms by which the expressed VSG gene is produced. The mechanisms of surface antigen diversity in trypanosomes may be of wide significance in other persistent infectious diseases where the biochemical basis of persistence is not as well defined.