MALARIA PARASITE LIGANDS AND HOST CELL RECEPTORS

疟疾的生命周期涉及受体特异性的相互作用，允许红细胞入侵和感染的红细胞与内皮细胞附着。这些特定事件是疫苗和药物干预的潜在目标。我们已经证明，在恶性疟原虫变异体抗原上，与间日疟原虫和恶性疟原虫红细胞入侵有关的相同基序是2-5个拷贝。我们正在确定这些基序是否参与了与内皮细胞和红细胞的黏附，以形成花环，这是一种致病标记。变异型抗原上的一个结构域与内皮细胞上的CD36结合。由于大多数寄生虫结合CD36，而主要的保护性免疫反应是针对这些变异抗原，因此有可能开发一种针对寄生虫这个区域的疫苗。虽然这是违反直觉的(变异是为了逃避免疫)，但这个结构域周围的表位通常不会诱导免疫，因为它们是隐蔽的，即在感染期间不具有免疫原性，但在接种疫苗后可以诱导保护。我们还在寻找其他影响红细胞入侵和内皮附着的受体。-恶性疟原虫、红细胞入侵、细胞黏附、妊娠

The life cycle of malaria involves receptor-specific interactions that allow invasion of red cells and attachment of infected red cells to endothelium. These specific events are potential targets for vaccines and drug interventions. We have demonstrated that the same motif involved in invading red cells for P. vivax and P. falciparum is found as two to five copies on the variant antigen of P. falciparum. We are determining if these motifs are involved in adhesion to endothelium and to red cells to form rosettes, a pathogenic marker. One of the domains on the variant antigen binds to CD36 on endothelium. As most parasites bind CD36 and the major protective immune response is to these variant antigens, it may be possible to develop a vaccine against this domain on the parasite. Although this is counterintuitive (variation is designed to escape immunity), the epitopes around this domain may not normally induce immunity because they are cryptic, that is, not immunogenic during infection, but protection can be induced after vaccination. We are also searching for other receptors for invasion of red cells and attachment to endothelium. - Plasmodium falciparum, red cell invasion, cytoadherence, pregnancy