Increased exposure to Plasmodium chabaudi antigens sustains cross-reactivity and avidity of antibodies binding Nippostrongylus brasiliensis: dissecting cross-phylum cross-reactivity in a rodent model.

Increased exposure to Plasmodium chabaudi antigens sustains cross-reactivity and avidity of antibodies binding Nippostrongylus brasiliensis: dissecting cross-phylum cross-reactivity in a rodent model.
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增加接触恰鲍迪疟原虫抗原可维持结合巴西圆线虫的抗体的交叉反应性和亲和力:在啮齿动物模型中剖析跨门交叉反应性。

DOI:
10.1017/s0031182015001390
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发表时间:
2015
期刊:
影响因子:
2.4
通讯作者:
Fairlie-Clarke KJ
Fairlie-Clarke KJ
中科院分区:
医学2区
文献类型:
--
作者:
Fairlie-Clarke KJ

文献摘要

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建立能够区分不同寄生虫并适当靶向不同寄生虫的抗体应答在宿主防御中至关重要。然而,识别(结合)多种寄生虫物种的交叉反应性抗体已得到充分证明。我们的目的是确定一个物种的更高剂量,从而在更长的时间内暴露于更大量的抗原,是否会微调对该物种的反应并减少交叉反应性。在BALB/c小鼠中使用夏氏疟原虫(Pcc)-巴西日本圆线虫(Nb)共感染模型,我们先前记录了交叉反应性抗体,我们在4个数量级上操纵Pcc的剂量。我们通过酶联免疫吸附试验、Western印迹和抗体耗竭试验研究了针对粗品和定义的重组抗原的抗原特异性和交叉反应性抗体应答。与我们的假设相反,即增加对Pcc的暴露会降低对Nb的交叉反应性,我们发现了识别共享抗原的抗体亚群的亲合力增加的证据。蛋白质印迹表明蛋白质的表观单体分子量28和98 kDa的Nb和PCC抗原制剂,也是一个Nb蛋白的重组PCC抗原,裂殖子表面蛋白-119的大小相似。本文讨论了与此类系统发育不同的寄生虫的抗原结合的抗体的影响。
Mounting an antibody response capable of discriminating amongst and appropriately targeting different parasites is crucial in host defence. However, cross-reactive antibodies that recognize (bind to) multiple parasite species are well documented. We aimed to determine if a higher inoculating dose of one species, and thus exposure to larger amounts of antigen over a longer period of time, would fine-tune responses to that species and reduce cross-reactivity. Using the Plasmodium chabaudi chabaudi (Pcc)–Nippostrongylus brasiliensis (Nb) co-infection model in BALB/c mice, in which we previously documented cross-reactive antibodies, we manipulated the inoculating dose of Pcc across 4 orders of magnitude. We investigated antigen-specific and cross-reactive antibody responses against crude and defined recombinant antigens by enzyme linked immunosorbent assay, Western blot and antibody depletion assays. Contrary to our hypothesis that increasing exposure to Pcc would reduce cross-reactivity to Nb, we found evidence for increased avidity of a subpopulation of antibodies that recognized shared antigens. Western blot indicated proteins of apparent monomer molecular mass 28 and 98 kDa in both Nb and Pcc antigen preparations and also an Nb protein of similar size to recombinant Pcc antigen, merozoite surface protein-119. The implications of antibodies binding antigen from such phylogenetically distinct parasites are discussed.