Goudot-Crozel V, Caillol D, Djabali M, Dessein A J
Centre d'Immunologie, INSERM-CNRS de Marseille-Luminy, France.
J Exp Med. 1989 Dec 1;170(6):2065-80. doi: 10.1084/jem.170.6.2065.
Schistosomiasis, due to Schistosoma mansoni, is a major health problem in many subtropical countries, and major efforts are being made to define a vaccine. In this regard, we have reported that sera from subjects with low susceptibility to infection by S. mansoni react with a major larval surface antigen (P-37), having an apparent molecular mass of 37 kD, against which sera of susceptible individuals show little reactivity. We have now cloned the cDNA for this antigen by screening a schistosome cDNA expression library with antibodies against the purified protein. The selected cDNAs encode a protein that is specifically identified by immune human sera containing antibodies against P-37, while sera exhibiting low or no reactivity toward P-37 fail to recognize the recombinant protein. The cloned cDNAs hybridize with a 1.2-kb RNA that is the transcript of a single copy gene. This RNA directs the synthesis of a 36.5-kD polypeptide that is precipitated by sera from the most resistant subjects. The amino acid sequence of the encoded polypeptide shows homology with the glycolytic enzyme Glyceraldehyde-3P-dehydrogenase (72.5% of positional identity with human Glyceraldehyde-3P-dehydrogenase). Antibodies against the recombinant protein identified P-37 on the larva. These findings, together with other reports, indicate that a number of conserved proteins may be major targets of host-protective immunity against S. mansoni. The hypothesis is discussed that genetic restriction of the immune response to these antigens may occur in heterogeneous human populations because of the limited number of T cell epitopes carried by these host-like proteins. Such genetic effects might allow parasite transmission through nonresponder (susceptible) individuals. This hypothesis and the protective properties of P-37 can now be tested using the recombinant protein and synthetic peptides derived from selected regions of the polypeptide chain.
由曼氏血吸虫引起的血吸虫病是许多亚热带国家的一个主要健康问题，目前正在大力研发疫苗。在这方面，我们已经报道，对曼氏血吸虫感染易感性较低的受试者的血清与一种主要的幼虫表面抗原（P-37）发生反应，该抗原的表观分子量为37kD，而易感个体的血清对此抗原几乎没有反应。我们现在通过用针对纯化蛋白的抗体筛选血吸虫cDNA表达文库，克隆了该抗原的cDNA。所选的cDNA编码一种蛋白质，该蛋白质可被含有抗P-37抗体的免疫人血清特异性识别，而对P-37反应低或无反应的血清则无法识别该重组蛋白。克隆的cDNA与一个1.2kb的RNA杂交，该RNA是一个单拷贝基因的转录本。这种RNA指导合成一种36.5kD的多肽，该多肽可被抵抗力最强的受试者的血清沉淀。编码多肽的氨基酸序列与糖酵解酶甘油醛-3-磷酸脱氢酶具有同源性（与人甘油醛-3-磷酸脱氢酶的位置同一性为72.5%）。针对重组蛋白的抗体在幼虫上鉴定出了P-37。这些发现以及其他报告表明，一些保守蛋白可能是宿主针对曼氏血吸虫保护性免疫的主要靶点。本文讨论了这样一个假说：由于这些宿主样蛋白携带的T细胞表位数量有限，在异质人群中可能会发生对这些抗原免疫反应的遗传限制。这种遗传效应可能使寄生虫通过无反应者（易感者）个体进行传播。现在可以使用重组蛋白和从多肽链选定区域衍生的合成肽来检验这一假说和P-37的保护特性。
