SURFACE CARBOHYDRATES OF PNEUMOCYSTIS CARINII

卡氏肺孢子虫肺炎是艾滋病患者的主要死亡原因 病人。在卡氏肺孢子虫发育过程中， 新发现的滋养体开始逐渐获得致密的电子 大衣。完全发育，囊内有一个突出的电子荧光体。 空间和一个涂层很厚的富含碳水化合物的外膜 抗原性。几种糖蛋白，包括116 kDa和 45-50种KDA，以及α-和β-葡聚糖，占 囊壁碳水化合物含量(8%)。卡氏肺孢子虫的结构 外膜被层发育过程中的碳水化合物，以及 成熟后，尚未阐明。它的结构是什么？ 糖蛋白的低聚糖链？什么是 葡聚糖的结构，以及它们与壁上的联系 糖蛋白？滋养体是否表现出独特的抗原性模式 成熟的包囊，这种变异是否与糖基化的差异有关？ 模式？人肺中有卡氏肺孢子虫特异性抗原吗？ 还是老鼠的肺？表面糖蛋白是否直接与 CD4+T细胞，如果是这样，碳水化合物在其中起重要作用吗 互动？葡聚糖除了结构上的作用外，还有其他作用吗？这个 拟议的研究将通过以下方式解决这些问题：1.确定 获得了gp116和gp45-50的寡糖链结构 来自老鼠和人类卡氏肺孢子虫滋养体和包囊。2.完全 葡聚糖等多糖的结构表征 在卡氏肺孢子虫的壁上发现。3.比较抗原模式和 分离的成熟包囊和成熟包囊碳水化合物的结构差异 滋养体糖蛋白，以及大鼠与人肺卡氏肺孢子虫。4. 检测卡氏肺孢子虫表面糖蛋白和/或碳水化合物 与CD4+T细胞结合。 建议研究的整体目标是分析 卡氏肺孢子虫包囊和滋养体表面的碳水化合物结构 通过比较两种发育阶段的糖基化模式来确定抗原 并确定这些碳水化合物是否参与了 调节宿主细胞的反应。所获得的数据将进一步推动我们的 对卡氏肺吸虫表面分子与其相互作用的认识 宿主细胞，并在计划新的治疗策略方面具有价值 艾滋病患者的卡氏肺孢子虫肺炎。

Pneumocystis carinii pneumonia is the leading cause of death in AIDS patients. During P. carinii development, the outer membrane of the newly excysted trophozoite gradually begins to acquire an electron-dense outer coat. Fully developed, the cyst bears a prominent electron-lucent space and a heavily coated, carbohydrate-rich outer membrane exhibiting antigenic activities. Several glycoproteins, including a 116 kDa and a 45-50 Kda species, along with alpha- and beta-glucans, account for the cyst wall carbohydrate content (8%). The structure of P. carinii carbohydrates during the development of the outer membrane coat, and after maturation, has not been elucidated. What are the structures of the oligosaccharide chains of the glycoproteins? What are the structures of the glucans, and how are they associated with the wall glycoproteins? Do trophozoites exhibit a unique antigenic pattern from mature cysts, and is this variation do to differences in glycosylation patterns? Are there antigens specific for P. carinii in human lungs versus rat lungs? Do the surface glycoproteins directly interact with CD4+T cells, and if so, do carbohydrates play a significant role in this interaction? Is there more than a structural role to the glucans? The proposed study will address these questions by: 1. Determining the structures of the oligosaccharide chains of gp116 and gp45-50, obtained from rat and human P. carinii trophozoites and cysts. 2. Completely characterizing the structure of the glucans and other polysaccharides found in the wall of P. carinii. 3. Comparing antigenic patterns and structural differences in carbohydrates of isolated mature cyst and trophozoite glycoproteins, and of rat versus human lung P. carinii. 4. Examining whether P. carinii surface glycoproteins and/or carbohydrates bind to CD4+T cells. The overall objective of the proposed studies is to analyze the carbohydrate structures of P. carinii cyst and trophozoite surface antigens by comparing glycosylation patterns of both developmental stages, and to determine if these carbohydrates are involved in mediating host cellular responses. The data obtained will further our understanding of the interactions of P. carinii surface molecules with host cells and be valuable in scheming new therapeutic tactics to combat P. carinii pneumonia in AIDS patients.