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B CELL & T CELL RECOGNITION SITES OF P FALCIPARUM GP195

B细胞

基本信息

批准号：
3454902
负责人：
Sandra Perreira Chang
金额：
$ 9.36万
依托单位：
UNIVERSITY OF HAWAII AT MANOA
依托单位国家：
美国
项目类别：
财政年份：
1989
资助国家：
美国
起止时间：
1989-07-01 至 1994-06-30
项目状态：
已结题

项目摘要

The major merozoite surface antigen (gp195) of P. falciparum and its analogues in several other Plasmodia induces a protective immune response in simian and murine hosts and is a prime candidate for a blood-stage malaria vaccine. Yeast recombinant gp195-based polypeptides are being developed as vaccine antigens. The efficacy of such vaccines is dependent on their ability to induce the appropriate antigen-specific B cells and to efficiently stimulate T cells which serve as helper/inducer cells in the antibody response or in antibody-independent immune responses. The specific aims of this project are (1) to define B cell recognition sites involved in the antibody responses to gp195 and gp195-related polypeptides and to determine whether H-2-linked immune response (Ir) genes control responsiveness to these recognition sites, (2) to define T cell recognition sites, study their regulation by Ir genes, and determine the surface phenotype of T cells induced by gp195 and recombinant gp195-related polypeptides and synthetic peptides, (3) to generate gp195-specific T cell lines and characterize their fine specificity and function (T helper activity, production of gamma interferon), and (4) to relate B cell and T cell recognition sites to variable, conserved, or group- specific regions of gp195 molecules. B cell recognition sites will be defined by immunization of mice with parasite-purified gp195 and gp195-related polypeptides and evaluation of serum antibody specificity by an ELISA assay. T cell recognition sites will be similarly defined using the antigen-induced proliferation assay or antigen-specific T helper cell assays. Antigens to be used for specificity analyses are (1) the homologous parasite-purified gp195: (2) a heterologous parasite-purified gp195 differing in group specific regions from the homologous protein; (3) recombinant gp195-related polypeptides corresponding to different fragments of the complete gp195 protein; and (4) synthetic peptides corresponding to variable repeat regions and to potential immuno- dominant B cell or T cell epitopes predicted by appropriate computer algorithms. The possible influence of Ir genes on responsiveness to B cell and T cell recognition sites will be studied by comparing the B cell and T cell recognition sites utilized by mice differing only at H-2 linked Ir genes. The characterization of T cell and B cell recognition sites as variable, conserved or group-specific is particularly relevant to vaccine design and will be accomplished by comparing antigen specificity for the homologous versus the heterologous gp195 protein.

恶性疟原虫的主要裂殖子表面抗原（gp 195），它在其他几种疟原虫中的类似物诱导了保护性免疫反应，是一个主要的候选者血液阶段的疟疾疫苗酵母重组gp 195 多肽被开发为疫苗抗原。疗效这类疫苗的有效性取决于它们诱导适当的抗原特异性B细胞并有效刺激在抗体中充当辅助/诱导细胞的T细胞反应或抗体非依赖性免疫反应。具体本项目的目的是（1）确定B细胞识别位点参与对gp 195和gp 195相关的抗体应答多肽，并确定H-2连接的免疫应答是否 (Ir)基因控制对这些识别位点的反应，（2）确定T细胞识别位点，研究Ir对T细胞识别位点的调节作用，基因，并确定诱导的T细胞表面表型 gp 195和重组gp 195相关多肽以及合成的（3）产生gp 195特异性T细胞系，表征其精细的特异性和功能（T辅助细胞活性，γ干扰素的产生），和（4）与相关B细胞和T细胞识别位点可变的，保守的，或组- GP 195分子的特定区域。 B细胞识别位点将通过用寄生虫纯化的gp 195免疫小鼠来定义和gp 195相关多肽以及血清抗体的评价特异性通过ELISA测定。 T细胞识别位点将被使用抗原诱导的增殖测定类似地定义，或抗原特异性T辅助细胞测定。抗原用于特异性分析是（1）同源寄生物纯化 gp 195：（2）异源寄生物纯化的gp 195，其不同之处在于同源蛋白质的组特异性区域;（3）重组 gp 195相关多肽对应于不同的完整的gp 195蛋白;和（4）合成肽对应于可变重复区和潜在的免疫- 优势B细胞或T细胞表位通过适当的计算机算法 Ir基因可能对对B细胞和T细胞识别位点的反应性将是通过比较B细胞和T细胞识别位点利用小鼠不同的只是在H-2连锁的Ir基因。的 T细胞和B细胞识别位点的表征可变的、保守的或组特异性的基因尤其与疫苗设计，并将通过比较抗原同源与异源gp 195的特异性蛋白