KEMRI-Wellcome Trust Collaborative Programme, Centre for Geographic Medicine Coast, Kilifi, Kenya.
PLoS One. 2012;7(1):e30095. doi: 10.1371/journal.pone.0030095. Epub 2012 Jan 17.
The Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) is a variant surface antigen expressed on mature forms of infected erythrocytes. It is considered an important target of naturally acquired immunity. Despite its extreme sequence heterogeneity, variants of PfEMP1 can be stratified into distinct groups. Group A PfEMP1 have been independently associated with low host immunity and severe disease in several studies and are now of potential interest as vaccine candidates. Although antigen-specific antibodies are considered the main effector mechanism in immunity to malaria, the induction of efficient and long-lasting antibody responses requires CD4+ T-cell help. To date, very little is known about CD4+ T-cell responses to PfEMP1 expressed on clinical isolates. The DBLα-tag is a small region from the DBLα-domain of PfEMP1 that can be amplified with universal primers and is accessible in clinical parasite isolates. We identified the dominant expressed PfEMP1 in 41 individual clinical parasite isolates and expressed the corresponding DBLα-tag as recombinant antigen. Individual DBLα-tags were then used to activate CD4+ T-cells from acute and convalescent blood samples in children who were infected with the respective clinical parasite isolate. Here we show that CD4+ T-cell responses to the homologous DBLα-tag were induced in almost all children during acute malaria and maintained in some for 4 months. Children infected with parasites that dominantly expressed group A-like PfEMP1 were more likely to maintain antigen-specific IFNγ-producing CD4+ T-cells than children infected with parasites dominantly expressing other PfEMP1. These results suggest that group A-like PfEMP1 may induce long-lasting effector memory T-cells that might be able to provide rapid help to variant-specific B cells. Furthermore, a number of children induced CD4+ T-cell responses to heterologous DBLα-tags, suggesting that CD4+ T-cells may recognise shared epitopes between several DBLα-tags.
疟原虫红细胞膜蛋白 1（PfEMP1）是成熟感染红细胞表面的一种变异表面抗原。它被认为是天然免疫的重要靶标。尽管 PfEMP1 的序列非常多样化，但它的变体可以分为不同的组。在几项研究中，A 组 PfEMP1 与低宿主免疫力和严重疾病独立相关，目前作为疫苗候选物具有潜在的研究价值。尽管抗原特异性抗体被认为是疟疾免疫的主要效应机制，但高效和持久的抗体反应的诱导需要 CD4+T 细胞的帮助。迄今为止，人们对临床分离株上表达的 PfEMP1 的 CD4+T 细胞反应知之甚少。DBLα-标签是 PfEMP1 的 DBLα-结构域的一个小区域，可以用通用引物扩增，并且在临床寄生虫分离株中是可及的。我们鉴定了 41 个个体临床寄生虫分离株中优势表达的 PfEMP1，并将相应的 DBLα-标签作为重组抗原进行表达。然后，使用个体 DBLα-标签来激活患有各自临床寄生虫分离株感染的急性和恢复期儿童的 CD4+T 细胞。在这里，我们表明，在几乎所有儿童的急性疟疾期间，同源 DBLα-标签诱导了 CD4+T 细胞反应，并在一些儿童中维持了 4 个月。与感染主要表达其他 PfEMP1 的寄生虫的儿童相比，感染主要表达 A 组样 PfEMP1 的寄生虫的儿童更有可能维持抗原特异性 IFNγ产生的 CD4+T 细胞。这些结果表明，A 组样 PfEMP1 可能诱导持久的效应记忆 T 细胞，这些细胞可能能够为变体特异性 B 细胞提供快速帮助。此外，许多儿童诱导了对异源 DBLα-标签的 CD4+T 细胞反应，表明 CD4+T 细胞可能识别几个 DBLα-标签之间的共同表位。
