DIFFERENTIAL SCREENING OF TRYPANOSOMA CRUZI ANTIGENS

查加斯病是一种由动质体原生动物克氏锥虫引起的潜在致命疾病。 这种生物体在大多数拉丁美洲国家流行，有1600万至1800万人感染，不仅对这些国家，而且对美国的血液供应构成威胁。大多数慢性感染者没有症状，终生处于疾病的所谓不确定阶段。 然而，在10- 30%的感染者中，会出现慢性恰加斯病典型的心脏和胃肠道表现。 T.本申请中提出的Cruzi抗原具有三个长期目标：（1.）了解发病机制中涉及的免疫过程，（2.）改进血清学诊断方法;以确定疫苗开发的潜在候选者。我们建议评估重组T。Cruzi抗原，它们在两组慢性感染的恰格曲病患者中引起的体液和细胞免疫应答：无症状的人和恰格曲病心肌病患者。 自1990年以来，这些患者一直在圣保罗大学医院的移植免疫学实验室进行研究。 通过用这些血清免疫筛选无鞭毛体cDNA文库，我们计划鉴定两组患者的免疫应答所识别的抗原。 将检测每种重组抗原与每例患者血清和外周血单核细胞（PMBC）的反应性。 我们假设将发现两类抗原：（a）刺激控制寄生虫感染的B-和/或T细胞应答的潜在保护性抗原，预期在无症状患者中更普遍的应答，和（B）交叉反应性抗原，其含有寄生虫和哺乳动物细胞共有的表位，使用来自具有可能的自身免疫反应的心脏病患者的血清将更可能鉴定出。 我们的研究将验证是否有抗体和/或细胞反应之间的相关性，以一些纯化的寄生虫抗原和T。克氏感染

Chagas disease is a potentially fatal disease caused by the kinetoplastid protzoan Trypanosoma cruzi. This organism is endemic in most Latin American countries where 16-18 million people are infected, and it constitutes a threat to the blood supply not only in those countries but also in the United States. The majority of chronically infected person are asymptomatic and remain for life in the so-called indeterminate phase of the disease. In 10-30 percent of infected individuals, however, cardiac and gastrointestinal manifestations typical of chronic Chagas disease occur. The study of T. cruzi antigens proposed in this application has three long-term objectives: (1.) to understand the immune processes involved in pathogenesis, (2.) to improve serological methods for diagnosis and (3.) to identify potential candidates for vaccine development. We propose to evaluate recombinant T. cruzi antigens for the humoral and cellular immune responses they elicit in two groups of chronically infected chagasic patients: asymptomatic persons and patients with chagasic cardiomyopathy. These patients have been studied in the Transplantation Immunology Laboratory of the Sao Paulo University Hospital since 1990. By immunoscreening an amastigote cDNA library with these sera, we plan to identify antigens that are recognized by the immune responses of the two groups of patients. Each recombinant antigen will be tested for its reactivity with sera and peripheral blood monocytes (PMBCs) derived from each patient. We hypothesize that two classes of antigens will be found: (a) potentially protective antigens that stimulate B- and/or T cell responses controlling the parasitic infection, responses expected to be more prevalent in asymptomatic patients, and (b) cross-reactive antigens containing epitopes shared by the parasite and mammalian cells that will be more likely identified using sera from cardiac patients with possible autoimmune reactions. Our studies will verify whether there is a correlation between the antibody and/or cellular response to a number of purified parasite antigens and the course of the T. cruzi infection.