Lacto-N-fucopentaose III (Lewis(X)), a target of the antibody response in mice vaccinated with irradiated cercariae of Schistosoma mansoni
Lacto-N-fucopentaose III (Lewis(X)), a target of the antibody response in mice vaccinated with irradiated cercariae of Schistosoma mansoni
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DOI：
10.1128/iai.64.5.1826-1831.1996
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发表时间：
1996-05-01
影响因子：
3.1
通讯作者：
Harn, DA
中科院分区：
文献类型：
--
作者：
Richter, D;Incani, RN;Harn, DA
曼氏血吸虫可溶性虫卵抗原上的碳水化合物是感染曼氏血吸虫病人和小鼠抗体应答的主要表位。最近，照射尾蚴免疫小鼠的保护性血清显示出识别糖体谷胱甘肽S-转移酶上的碳水化合物表位。本研究表明，糖抗原表位是15或50千拉德照射的血吸虫尾蚴免疫C57 BL/6 J和CBA/J小鼠血清的主要靶点。mansoni对碳水化合物表位的抗体滴度随着接种次数的增加而增加，并且在C57 BL/6 J小鼠中比在CBA/J小鼠中显著更高。通过测量抗体与已知存在于寄生虫上的限定寡糖残基的结合来确定这种抗碳水化合物反应的特异性。免疫小鼠体液抗碳水化合物反应的主要靶标是乳糖-N-岩藻五糖III，一种与细胞运输相关的分子。我们观察到没有结合到其非岩藻糖基化同系物，乳糖-N-新四糖，或存在于匙孔血蓝蛋白的寡糖。在用15千拉德辐照的尾蚴重复接种的C57 BL/6 J和CBA/J小鼠中观察到对乳糖-N-岩藻五糖III的最强抗体应答，这也达到了最高水平的保护。免疫球蛋白M是与乳糖-N-岩藻五糖III结合的主要抗体类别。我们的结论是，在辐照尾蚴疫苗模型中，C57 BL/6 J和CBA/J小鼠产生针对不同阶段的S. mansoni，低聚糖乳糖-N-岩藻五糖III是这种反应的一个靶点。乳糖-N-岩藻五糖III及其特异性抗体可能深刻影响宿主抗性和寄生虫归巢。
Carbohydrates on soluble egg antigens are major epitopes for the antibody responses of patients and mice infected,vith Schistosoma mansoni. Recently, protective sera of mice vaccinated with irradiated cercariae were shown to recognize carbohydrate epitopes on schistosomal glutathione S-transferase. The present study demonstrates that carbohydrate epitopes are major targets of sera from C57BL/6J and CBA/J mice vaccinated with 15- or 50-kilorad-irradiated cercariae of S. mansoni. Antibody titers to carbohydrate epitopes increased with the number of vaccinations and were considerably higher in C57BL/6J mice than in CBA/J mice, The specificity of this anticarbohydrate response was determined by measuring antibody binding to defined oligosaccharide residues known to be present on the parasite. A predominant target of the humoral anticarbohydrate response of vaccinated mice was lacto-N-fucopentaose III, a molecule relevant for cell trafficking. We observed no binding to its nonfucosylated homolog, lacto-N-neotetraose, or to oligosaccharides present on keyhole limpet hemocyanin. The strongest antibody response to lacto-N-fucopentaose III was observed for C57BL/6J and CBA/J mice repeatedly vaccinated with 15-kilorad-irradiated cercariae, which also achieve the highest levels of protection. Immunoglobulin M was the predominant antibody class binding to lacto-N-fucopentaose III. We conclude that in the irradiated-cercaria vaccine model, C57BL/6J and CBA/J mice produce anticarbohydrate antibodies against various stages of S. mansoni and that the oligosaccharide lacto-N-fucopentaose III is one target of this response. Lacto-N-fucopentaose III and its specific antibodies may profoundly affect host resistance and parasite homing.