STRUCTURE AND EXPRESSION OF PNEUMOCYSTIS ANTIGEN GENES

肺孢子虫抗原基因的结构和表达

• 批准号: 2073149
• 负责人: JAMES Richard STRINGER
• 金额: $ 19.49万
• 依托单位: UNIVERSITY OF CINCINNATI
• 依托单位国家: 美国
• 财政年份: 1995
• 资助国家: 美国
• 起止时间: 1995-08-01 至 1999-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2073149
• 关键词: Pneumocystis carinii; gene expression; genetic polymorphism; laboratory rat; nucleic acid sequence; protozoal antigen

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.

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中引起肺炎，并且是 艾滋病患者的发病率。卡氏疟原虫含有一个基因家族， 编码一个名为主要表面抗原的大家族 大鼠和人卡氏肺孢子虫中的糖蛋白（MSG）和卡氏肺孢子虫中的gpA 从雪貂。基因家族的复杂性赋予卡氏肺吸虫 在个体表面呈现各种结构的可能性 微生物，引起怀疑，味精的变化可能起作用， 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 生物体在哺乳动物肺中生存的能力。最近 大鼠单克隆抗体研究的结果表明， 表达以两种方式变化：（i）不是种群中的所有生物体 在同一时间表达相同的味精。(ii)某些MSG表位 在一些种群中大量存在，而在另一些种群中检测不到。尽管 卡氏肺孢子虫具有多种抗原伪装、免疫 这种微生物是规范，这鼓励了发展的希望， 免疫治疗和疫苗接种程序。此外，味精不太可能 仅作为抗原发挥作用，并破坏生产或 MSG的功能可能是治疗性的。这些领域的进展将需要 了解生物体改变其表面的能力 抗原，这将需要了解的结构和 MSG基因家族的表达。的重要线索 MSG变异的机制最近出现。大多数味精mRNA开始 具有相同的前导序列（LS），但该序列不存在于 90%的卡氏肺吸虫染色体都含有MSG基因。 对含有LS的基因组DNA片段的分析表明， 与至少8种不同的MSG基因相邻，可能更多。这些 研究人员根据数据推测， 在一个单一的网站（LS），并在一个表达的MSG基因， 特定的生物体可以通过MSG基因之间的重组而改变， LS基因座和位于别处的数十个MSG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MSG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 大鼠模型的变化。