HUMAN T-CELL RECOGNITION OF THE CIRCUMSPOROZOITE PROTEIN OF PLASMODIUM-FALCIPARUM - IMMUNODOMINANT T-CELL DOMAINS MAP TO THE POLYMORPHIC REGIONS OF THE MOLECULE

HUMAN T-CELL RECOGNITION OF THE CIRCUMSPOROZOITE PROTEIN OF PLASMODIUM-FALCIPARUM - IMMUNODOMINANT T-CELL DOMAINS MAP TO THE POLYMORPHIC REGIONS OF THE MOLECULE
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DOI:
10.1073/pnas.85.4.1199
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发表时间:
1988-02-01
影响因子:
11.1
通讯作者:
MILLER, LH
MILLER, LH
中科院分区:
综合性期刊1区
文献类型:
--
作者:
GOOD, MF;POMBO, D;MILLER, LH

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如果目标是在感染期间增强抗体或刺激抗体非依赖性T细胞免疫,那么人类T细胞抗原位点的定义对肽免疫原亚单位疫苗的开发是重要的。为了确定恶性疟原虫环子孢子(CS)蛋白上的这些位点,我们制作了29个跨越整个CS蛋白的重叠合成肽,并测试了它们刺激居住在西非恶性疟原虫流行区的35名成年人的外周血淋巴细胞的能力。有3个免疫优势结构域位于重复区之外。然而,这些结构域发生在分子的多态区域,这表明寄生虫的突变和选择是对来自T细胞的免疫压力的反应。这种多态可能会给疫苗开发带来障碍。
The definition of human T-cell antigenic sites is important for subunit vaccine development of a peptide immunogen if the goal is to allow antibody boosting during infection or to stimulate antibody-independent T-cell immunity. To identify such sites on the circumsporozoite (CS) protein of Plasmodium falciparum, 29 overlapping synthetic peptides spanning the entire CS protein were made and tested for their ability to stimulate peripheral blood lymphocytes from 35 adults living in a P. falciparum malria-endemic region of West Africa. Three immunodominant domains were located outside the repetitive region. These domains, however, occurred in the polymorphic regions of the molecule, suggesting that parasite mutation and selection has occurred in response to immune pressure from T cells. Such polymorphism may impose an obstacle for vaccine development.