MECHANISMS OF ANTIGENIC DIVERSITY IN TRYPANOSOMA BRUCEI

锥虫病严重制约着人类和畜牧业的发展。 在非洲的许多地方。对寄生虫的免疫力的发展是 无效，因为抗原变异，由于一个序列的变化 表面糖蛋白(可变表面糖蛋白或VSG)。基因 VSG的编码可以快速发展。因此，特定的VSG基因可能 在许多不同的股票中或仅在几个股票中有代表性。此外，VSG 基因可以在每个种群中以相同的副本存在，也可以作为部分副本存在 同源基因拷贝。生物多样性产生的分子机制 血管紧张素转换酶基因谱系尚不清楚，尽管有证据表明 基因转化和点突变均可获得。锥虫有 都是从相同的血清型分离出来的，这些血清型具有可变的 暴露的表面表位。VSG基因在这些锥虫体内的表达 可能是进化中的基因的例子，其序列关系与 祖先有机体仍然是显而易见的。人血管紧张素基因的结构 将先祖生物体和相关后代中的 提示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。 这一方法将涉及从祖细胞中克隆VSG基因和cDNA 锥虫和血清学后代。克隆的DNA将是 通过限制性内切酶和S1核酸酶图谱进行比较。具体目标 包括： (A)从1个布氏锥虫克隆种群中分离出5个克隆种群 共享暴露表面表位的血清学； (B)确定基因的完整基本拷贝是否对 五个相关的VSG中的每一个都预先存在于祖细胞中 有机体；以及 (C)在祖细胞生物体中不存在完整的碱基拷贝的情况下， 确定表达的VSG基因的产生机制。 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所在 持久力的基础没有得到很好的定义。

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.