Small, clonally variant antigens expressed on the surface of the Plasmodium falciparum-infected erythrocyte are encoded by the rif gene family and are the target of human immune responses.
Small, clonally variant antigens expressed on the surface of the Plasmodium falciparum-infected erythrocyte are encoded by the rif gene family and are the target of human immune responses.
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在恶性疟原虫感染的红细胞表面表达的较小的克隆变异抗原由RIF基因家族编码，并且是人类免疫反应的靶标。
DOI：
10.1084/jem.190.10.1393
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发表时间：
1999-11-15
影响因子：
15.3
通讯作者：
Wahlgren, M
中科院分区：
文献类型：
--
作者：
Fernandez, V;Hommel, M;Chen, Q;Hagblom, P;Wahlgren, M
恶性疟原虫感染的疾病严重程度是寄生虫有效逃避人类宿主防御机制的直接后果。迄今为止，已知一种寄生虫衍生的分子，即抗原性变体粘附素恶性疟原虫红细胞膜蛋白1（PfEMP 1），被转运到感染的红细胞（pRBC）表面，在那里它介导与不同宿主受体的结合。在这里，我们报告，多个额外的蛋白质表达的寄生虫在pRBC表面，包括一个大簇的克隆变异抗原的30-45 kD。我们发现这些抗原与rifins相同，rifins是由rif多基因家族编码的预测多肽。这些寄生虫产物，在它们在玫瑰花结寄生虫中被鉴定后，以前被称为玫瑰花结素，在恶性疟原虫的新鲜分离株中显著表达。Rifins在自然感染中具有免疫原性，并且在表面标记的pRBC提取物的免疫沉淀中被人免疫血清特异性识别。此外，人免疫血清在未检测到放射性碘标记PfEMP 1多肽但检测到rifins的条件下凝集用胰蛋白酶消化的pRBC，表明凝集抗体靶向rifins中存在表位。当通过二维电泳分析时，rifins在pI 5.5-6.5范围内分解为几种同种型，表明分子微异质性，这是恶性疟原虫抗原多样性的另一个潜在的新来源。20，22，76-80，140，和170 kD的突出的多肽也检测到pRBC的表面轴承在体外繁殖或现场分离的寄生虫。在这份报告中，我们描述了rifins，已知被恶性疟原虫展示在感染的红细胞表面的克隆变异抗原的第二个家庭。
Disease severity in Plasmodium falciparum infections is a direct consequence of the parasite's efficient evasion of the defense mechanisms of the human host. To date, one parasite-derived molecule, the antigenically variant adhesin P. falciparum erythrocyte membrane protein 1 (PfEMP1), is known to be transported to the infected erythrocyte (pRBC) surface, where it mediates binding to different host receptors. Here we report that multiple additional proteins are expressed by the parasite at the pRBC surface, including a large cluster of clonally variant antigens of 30–45 kD. We have found these antigens to be identical to the rifins, predicted polypeptides encoded by the rif multigene family. These parasite products, formerly called rosettins after their identification in rosetting parasites, are prominently expressed by fresh isolates of P. falciparum. Rifins are immunogenic in natural infections and strain-specifically recognized by human immune sera in immunoprecipitation of surface-labeled pRBC extracts. Furthermore, human immune sera agglutinate pRBCs digested with trypsin at conditions such that radioiodinated PfEMP1 polypeptides are not detected but rifins are detected, suggesting the presence of epitopes in rifins targeted by agglutinating antibodies. When analyzed by two-dimensional electrophoresis, the rifins resolved into several isoforms in the pI range of 5.5–6.5, indicating molecular microheterogeneity, an additional potential novel source of antigenic diversity in P. falciparum. Prominent polypeptides of 20, 22, 76–80, 140, and 170 kD were also detected on the surfaces of pRBCs bearing in vitro–propagated or field-isolated parasites. In this report, we describe the rifins, the second family of clonally variant antigens known to be displayed by P. falciparum on the surface of the infected erythrocyte.