STRUCTURE AND EXPRESSION OF PNEUMOCYSTIS ANTIGEN GENES

描述：(改编自申请人摘要)。卡氏肺孢子虫 在免疫功能低下的人类中引起肺炎，是导致 艾滋病患者的发病率。卡氏肺孢子虫包含一个基因家族， 编码一大类表面抗原，命名为主要表面 大鼠和人卡氏肺吸虫的糖蛋白(MSG)和卡氏肺吸虫的GPA 从雪貂身上。基因家族的复杂性赋予了卡氏肺孢子虫 在个体的表面呈现各种结构的潜力 微生物，这让人怀疑味精的变异可能起到 帮助卡氏肺孢子虫逃避宿主免疫系统，和/或以其他方式增加 机体在哺乳动物肺中生存的能力。近期 对大鼠的单抗研究结果表明，味精 表达有两个方面的差异：(I)不是种群中的所有生物体 同时表达相同的消息。(Ii)某些味精表位是 在一些种群中大量存在，在其他种群中检测不到。尽管 卡氏肺孢子虫可能采用多种抗原伪装，免疫 对于这种微生物来说，这是一种规范，它鼓励了发展的希望 免疫治疗和疫苗接种程序。此外，消息不太可能 仅作为抗原发挥作用，并扰乱生产或 味精的功能可能具有治疗作用。在这些领域取得进展将需要 对有机体改变其表面的能力的理解 抗原，这将需要了解结构和 味精基因家族的表达。一条重要的线索 最近出现了味精变异的机制。大多数味精mRNAs开始于 具有相同的前导序列(LS)，但该序列不存在于 卡氏肺孢子虫90%的染色体都含有味精基因。 对含有LS的基因组DNA片段的分析表明，它是 与至少8种不同的味精基因相邻，甚至更多。这些 数据引导研究人员假设表达的味精基因驻留在 在单个位置(LS)，并且在一个 特定的生物体可以通过味精基因之间的重组而改变 LS基因和位于其他地方的几十个味精基因中的一个或多个 在基因组中。为了验证这一假设，他们提出了以下建议 具体目标..。1.确定味精基因座的结构。2.确定 它们在抗原变异中的作用。3.味精的动力学分析 大鼠模型的变异。

DESCRIPTION: (Adapted from Applicant's Abstract). Pneumocystis carinii causes pneumonia in immunocompromised humans, and is a leading cause of morbidity among AIDS patients. P. carinii contains a gene family which encodes a large family of surface antigens named Major Surface Glycoprotein (MSG) in rat and human P. carinii, and gpA in P. carinii from ferrets. The complexity of the gene family endows P. carinii with the potential to present various structures on the surface of individual organisms, raising the suspicion that variation in MSG may function to help P. carinii escape the host immune system, and/or otherwise increase the capacity of the organism to survive in the mammalian lung. Recent results of monoclonal antibody studies in rats have shown that MSG expression varies in two ways: (i) not all organisms in a population express the same MSGs at the same time. (ii) certain MSG epitopes are abundant in some populations and undetectable in others. Despite the potential of P. carinii to adopt a variety of antigenic guises, immunity to this microbe is the norm, which encourages hopes for development of immunotherapy and vaccination procedures. In addition, MSGs are unlikely to function solely as antigens, and disruption of the production or fuction of MSGs may be therapeutic. Progress in these areas will require an understanding of the capacities of the organism to change its surface antigens, which will require understanding of the structure and expression of the family of MSG genes. An important clue to the mechanism of MSG variation has recently emerged. Most MSG mRNAs begin with the same leader sequence (LS), but this sequence is not present on 90% of the P. carinii chromosomes, all of which contain MSG genes. Analysis of genomic DNA fragments containing the LS showed that it is adjacent to at least 8 different MSG genes, and probably more. These data lead investigators to hypothesize that expressed MSG genes reside at a single site (LS), and that the MSG genes that are expressed in a given organism can be changed by recombination between MSG genes at the LS locus and one or more of the dozens of MSG genes located elsewhere in the genome. To test this hypothesis they propose the following specific aims... 1. Determine the structures of MSG loci. 2. Determine their role in antigenic variation. 3. Analyze the dynamics of MSG variation in the rat model.