Identification of a 67-amino-acid region of the Plasmodium falciparum variant surface antigen that binds chondroitin sulphate A and elicits antibodies reactive with the surface of placental isolates
Identification of a 67-amino-acid region of the Plasmodium falciparum variant surface antigen that binds chondroitin sulphate A and elicits antibodies reactive with the surface of placental isolates
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DOI：
10.1111/j.1365-2958.2004.04145.x
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发表时间：
2004-07-01
影响因子：
3.6
通讯作者：
Miller, LH
中科院分区：
文献类型：
--
作者：
Gamain, B;Smith, JD;Miller, LH
孕期疟疾的并发症是由胎盘中大量隔离寄生的红细胞(PE)引起的。恶性疟原虫胎盘分离株的不同寻常之处在于，它们不结合初级微血管受体CD36，而是结合硫酸软骨素A(CsA)。孕妇产生的抗体可以识别世界各地的胎盘变异，这表明预防怀孕期间疟疾的疫苗是可能的。恶性疟原虫红细胞膜蛋白-1(PfEMP-1)家族的部分成员在中国仓鼠卵巢(CHO)细胞上表达时，可与CsA结合。为了更好地表征DBL-Gamma与CsA黏附的分子要求，我们确定了各种DBL-Gamma结构域的结合。大多数DBL-γ不与CsA结合，也没有发现严格区分结合和非结合的保守区。FCR3-CsA DBL-Gamma结构域的结构-功能分析将最小的CSA结合区定位为67个残基片段。该区域在一些结合序列中部分保守。用最小结构域免疫的兔血清与CsA结合的寄生虫系反应，但不与CD36和其他受体结合的非CsA粘附性PE系反应。从高度可变的细胞黏附家族中识别最小结合区可能应用于妊娠期疟疾疫苗。
The complications of malaria in pregnancy are caused by the massive sequestration of parasitized erythrocytes (PE) in the placenta. Placental isolates of Plasmodium falciparum are unusual in that they do not bind the primary microvasculature receptor CD36 but instead bind chondroitin sulphate A (CSA). Pregnant mothers develop antibodies that recognize placental variants worldwide, suggesting that a vaccine against malaria in pregnancy is possible. Some members of the Duffy binding-like gamma (DBL-gamma) domain of the large and diverse P. falciparum erythrocyte membrane protein-1 (PfEMP-1) family, when expressed on Chinese hamster ovary (CHO) cells, bind CSA. To characterize better the molecular requirements for DBL-gamma adhesion to CSA, we determined the binding of various DBL-gamma domains. Most DBL-gamma did not bind CSA, and no conserved region was identified that strictly differentiated binders from non-binders. Structure-function analysis of the FCR3-CSA DBL-gamma domain localized the minimal CSA binding region to a 67-residue fragment. This region was partially conserved among some binding sequences. Serum from a rabbit immunized with the minimal domain reacted with CSA-binding parasite lines, but not with non-CSA-adherent PE lines that adhered to CD36 and other receptors. The identification of a minimal binding region from a highly variable cytoadherent family may have application for a vaccine against malaria in pregnancy.