Fairlie-Clarke Karen J, Hansen Christina, Allen Judith E, Graham Andrea L
Institutes of Evolution,Immunology and Infection Research,School of Biological Sciences,King's Buildings,University of Edinburgh,Edinburgh,UK.
Department of Ecology and Evolutionary Biology,Princeton University,Princeton,NJ,USA.
Parasitology. 2015 Dec;142(14):1703-14. doi: 10.1017/S0031182015001390. Epub 2015 Oct 22.
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-1(19). The implications of antibodies binding antigen from such phylogenetically distinct parasites are discussed.
产生能够区分并适当靶向不同寄生虫的抗体反应对宿主防御至关重要。然而,识别(结合)多种寄生虫物种的交叉反应性抗体已有充分记载。我们旨在确定一种物种更高的接种剂量,从而在更长时间内接触大量抗原,是否会微调对该物种的反应并降低交叉反应性。我们使用BALB/c小鼠的恰氏疟原虫(Pcc)-巴西日圆线虫(Nb)共感染模型(我们之前在该模型中记录到了交叉反应性抗体),将Pcc的接种剂量在4个数量级范围内进行调整。我们通过酶联免疫吸附测定、蛋白质印迹和抗体清除试验,研究了针对粗制和特定重组抗原的抗原特异性及交叉反应性抗体反应。与我们关于增加对Pcc的接触会降低对Nb的交叉反应性的假设相反,我们发现有证据表明识别共同抗原的抗体亚群的亲和力增加。蛋白质印迹显示,Nb和Pcc抗原制剂中均有表观单体分子量为28和98 kDa的蛋白质,还有一种与重组Pcc抗原裂殖子表面蛋白-1(19)大小相似的Nb蛋白。本文讨论了抗体结合来自这种系统发育上不同的寄生虫的抗原的意义。