IMMUNE RESPONSE TO CLONED SCHISTOSOME ANTIGENS

对克隆血吸虫抗原的免疫反应

• 批准号: 3453943
• 负责人: JOHN S CORDINGLEY
• 金额: $ 9.75万
• 依托单位: UNIVERSITY OF WYOMING
• 依托单位国家: 美国
• 财政年份: 1988
• 资助国家: 美国
• 起止时间: 1988-04-01 至 1993-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3453943
• 关键词: DNA footprinting; Schistosoma; antigen antibody reaction; biological polymorphism; clone cells; complementary DNA; drug design /synthesis /production; enzyme linked immunosorbent assay; gene expression; genetic manipulation; helminthic antigen; high performance liquid chromatography; human subject; immune response genes; immunological substance; immunoprecipitation; immunosuppression; laboratory mouse; laboratory rabbit; nucleic acid probes; nucleic acid sequence; protein engineering; protozoal vaccine; radionuclides; synthetic antigens; synthetic vaccines

The aim of this research is to understand the nature of immune response defects to parasite antigens as an aid to the future rational design of parasite vaccines. We will investigate the nature of immune response gene defects in inbred mice using previously isolated cDNA clones of S.mansoni antigens. Subsequently, using human patients in family groups we will attempt to establish to what extent the observed variation in the human immune response has a genetic basis. The antibody responses to S.mansoni infection in mice are under genetic control. We have shown that the responses to particular antigens are regulated by genes in the MHC and elsewhere in the genome. Several possible mechanisms are proposed to account for this. Antigens will be produced in E.coli both as full length molecules and as partial deletion products and used as antigens and immunogens to identify possible regions of the antigen molecules responsible for suppression of the immune response. Hybrid antigens made by the fusion of two genes or subgenomic fragments will be used to test for suppression directed against particular parts of a polypeptide or to improve the immunogenicity of certain antigens. Using purified antigens we will determine whether the immune response gene effects are a consequence of infection or a property of the antigens themselves. Routes of antigen presentation will be varied to assess the role this plays in the immune response gene effects. Experimental immunizations with purified antigen during chronic infection will reveal induced suppressive effects should they exist. Panels of recombinant antigens and synthetic peptides will be used as antigens to fingerprint the immune responses of human patients in family studies to identify potential genetic influences on the human immune response. We will compare the antibody responses of infected mice with those induced by vaccination with irradiated cercariae and by immunization with recombinant and synthetic antigens. The responses will be compared both in terms of the epitopes recognized and the isotypes of antibody produced to each antigen. Further schistosome antigen clones relevant to immunity will be sought by a number of approaches. Suitable synthetic and recombinant antigens will be tested for their ability to induce immunity in experimental animals.

这项研究的目的是了解免疫的本质 寄生虫抗原的反应缺陷以帮助未来 寄生虫疫苗的合理设计。 我们将研究免疫反应基因缺陷的性质 使用先前隔离的s.mansoni的染色小鼠 抗原。 随后，在家庭组中使用人类患者我们 将尝试确定观察到的变化的程度 人免疫反应具有遗传基础。 小鼠中对麦克索尼感染的抗体反应在 遗传控制。 我们已经证明了对特定的回应 抗原受到MHC和其他地方的基因调节 基因组。 提出了几种可能的机制来考虑 这。 抗原将在E.Coli中产生，均为全长 分子和部分缺失产物，用作抗原 和免疫原以鉴定抗原的可能区域 负责抑制免疫反应的分子。 由两个基因或亚基因组融合制成的杂化抗原 片段将用于测试针对的抑制 多肽的特定部分或改善 某些抗原的免疫原性。 使用纯化的抗原，我们将确定免疫是否 反应基因效应是感染或A的结果 抗原本身的财产。 抗原路线 演讲将有所不同，以评估这种作用 免疫反应基因效应。 实验免疫 慢性感染期间纯化的抗原将显示诱导 抑制作用应该存在。 重组面板 抗原和合成肽将用作抗原 指纹在家庭中人类患者的免疫反应 研究以确定对人类的潜在遗传影响 免疫反应。 我们将比较感染小鼠的抗体反应 那些因辐照cercariae和 重组和合成抗原免疫。 这 将根据表位比较两个响应 识别和每种抗原产生的抗体的同种型。 与免疫相关的进一步的血吸虫抗原克隆将是 通过多种方法寻求。 合成的合成和 重组抗原的诱导能力将测试 实验动物的免疫力。