BIOLOGICAL AND BIOCHEMICAL STUDIES OF ANTIGENS ON MALARIA-INFECTED RED CELLS

我们正在研究插入的疟疾蛋白的结构和功能 进入和穿过感染成熟无性生殖的红细胞膜 疟疾寄生虫和内皮细胞上的分子参与了 细胞黏附。 两个非常大的(mV约30万)恶性疟原虫蛋白已经被 定位于感染的红细胞膜。一种蛋白质是 暴露在细胞表面，并似乎中介附着到 内皮细胞。另一种疟疾蛋白定位于 调节细胞黏附的旋钮突起处的膜。这些 蛋白质似乎在结构上没有关联。第三种恶性疟原虫 组氨酸含量异常高的蛋白质也定位于 旋钮下的亚膜材料。富含组氨酸的蛋白质是一种 旋钮的结构或功能组件，但不直接授予 细胞黏附。 西非恶性疟原虫分离株的免疫电子显微镜研究 患者已经证明，分离株特异性和泛特异性细胞表面 由同源和异种非洲血清定义的表位都是 定位在旋钮突起上。 凝血酶敏感蛋白作为宿主细胞配体的潜在作用 对细胞黏附进行了更详细的研究。的阶段性 感染细胞对凝血酶敏感蛋白的黏附和胰酶敏感性 被感染的细胞表面成分，与这种蛋白质的结合有关 与内皮细胞的附着特性相匹配。我们还有 表明参与肝素结合的凝血酶原蛋白的结构域不是 与感染的红细胞的附着有关。 我们还对两个恶性疟原虫编码蛋白的基因进行了测序。 非同寻常的组氨酸含量，其中之一是通过主机输出的 红细胞表面膜进入血浆。

We are studying the structure and function of malarial proteins inserted into and though the membrane of erythrocytes infected with mature asexual malaria parasites and molecules on the endothelial cells involved in cytoadherence. Two very large (Mv about 300,000) P. falciparum proteins have been localized to the surface membrane of infected erythrocytes. One protein is exposed on the cell surface and appears to mediate attachment to endothelial cells. The other malarial protein is localized under the membrane at the knob protrusions which mediate cytoadherence. These proteins do not appear to be related structurally. A third P. falciparum protein of unusually high histidine content has also been localized to the submembrane material under knobs. The histidine-rich protein is a structural or functional component of knobs but does not directly confer cytoadherence. Immunoelectonmicroscopy studies of P. falciparum isolates from West African patients have shown that the isolate-specific and pan-specific cell surface epitopes defined by homologous and heterologous African sera are both localized on the knob protrusions. The potential role of thrombospondin as the host cell ligand for cytoadherence has been studied in more detail. The stage-specificity of attachment of infected cells to thrombospondin and trypsin-sensitivity of the infected cell surface component involved in attachment to this protein match the properties of attachment to endothelial cells. We have also shown that the domain of thrombospondin involved in heparin binding is not involved in attachment of infected erythrocytes. We have also sequenced two P. falciparum genes encoding proteins of extraordinary histidine content, one of which is exported through the host erythocyte surface membrane into the plasma.