T CELL EPITOPES OF THE MALARIA CS PROTEINS

对疟疾寄生虫子孢子阶段的免疫是T细胞 依赖机制和效应机制包括体液机制和细胞机制 介导的免疫反应。一种免疫优势B细胞表位 疟疾寄生虫的环子孢子(CS)蛋白的 是用两种病毒产生的抗子孢子抗体来定义的 自然感染和实验免疫的宿主。这个 活化T细胞的抗原决定簇 抗子孢子免疫反应尚未确定。这个 这项拟议的研究的目标是确定人的T细胞表位 CS蛋白在保护性免疫诱导中的作用 豁免权。不同品系小鼠的细胞免疫 啮齿动物疟疾的子孢子，P.berghei，将在 合成和重组CS蛋白类似物的体外实验 并将尝试定义一种体外试验，该试验 与体内的保护相关。T细胞系和克隆将是 从免疫小鼠中分离T细胞以研究T细胞的精细特异性 以及单克隆性T细胞群的免疫功能。 含有T细胞的合成肽或重组蛋白 表位和免疫优势B细胞表位(S)。 Berghei CS蛋白将用于免疫各种类型的小鼠 以测试这些CS抗原构建物的能力 在体内诱导保护。 小鼠的同源菌株也将被用来定义T细胞 人间日疟原虫CS蛋白表位(S)这个 小鼠T细胞抗间日疟原虫克隆的良好特异性 与来自生活在中国的人的T细胞克隆相比 流行间日疟原虫的地区。关于T的识别 CS蛋白的细胞表位(S)将有助于设计 一种有效诱导细胞介导AS的子孢子疫苗 以及体液免疫。这些研究还将确立 保护性免疫测定的最佳体外试验(S) 提供一种监控功能开发的方法 自然感染人群中的抗子孢子免疫反应 接种疫苗的宿主。

Immunity to the sporozoite stage of the malaria parasite is T cell dependent and effector mechanism include both humoral and cell mediated immune responses. An immunodominant B cell epitope of the circumsporozoite (CS) protein of the malaria parasite has been defined using antisporozoite antibodies produced in both naturally infected and experimentally immunized hosts. The antigenic determinants which activate T cells during an antisporozoite immune response have not yet been identified. The goal of the proposed research is to identify the T cell epitopes of the CS protein which function in the induction of protective immunity. Cells of various strains of mice immunized with sporozoite of the rodent malaria, P. berghei, will be challenged in vitro with synthetic and recombinant analogues of the CS protein and attempts will be made to define an in vitro assay which correlates with protection in vivo. T cell lines and clones will be isolated from the immunized mice to study T cell fine specificity and the immune function of monoclonal T cell populations. Synthetic peptides or recombinant proteins containing the T cell epitopes and the immunodominant B cell epitope(s) of the P. berghei CS protein will be used to immunize mice of various strains to test for the ability of these CS antigen constructs to induce protection in vivo. Murine congenic strains will also be used to define the T cell epitope(s) of the CS proteins of the human malaria, P. vivax. the fine specificity of murine T cell anti vivax clones will be compared to human T cell clones derived from individuals living in areas of endemic P. vivax malaria. The identification of the T cell epitope(s) of the CS protein will facilitate the design of a sporozoite vaccine which effectively induces cell mediated as well as humoral immunity. The studies will also establish the optimal in vitro assay(s) for measuring protective immunity and provide a means of monitoring the development of functional antisporozoite immune responses in naturally infected or vaccinated hosts.