MALARIA PARASITE LIGANDS AND HOST CELL RECEPTORS

疟疾的生命周期涉及受体特异性相互作用，使红细胞侵入并使受感染的红细胞附着于内皮。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，在恶性疟原虫的变异抗原上发现了与间日疟原虫和恶性疟原虫侵入红细胞有关的相同基序，为2至5个拷贝。我们正在确定这些基序是否参与粘附到内皮细胞和红细胞上，以形成一种致病标记物roxylase。变体抗原上的一个结构域结合内皮上的CD36。由于大多数寄生虫结合CD36，并且主要的保护性免疫应答是针对这些变体抗原，因此可能开发针对寄生虫上的该结构域的疫苗。尽管这是违反直觉的（变异是为了逃避免疫），但该结构域周围的表位通常可能不会诱导免疫，因为它们是隐蔽的，即在感染期间没有免疫原性，但在接种疫苗后可以诱导保护。我们也在寻找其他受体，用于红细胞的侵袭和内皮细胞的粘附。- 恶性疟原虫，红细胞侵袭，细胞粘附，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