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Analysis of the OspE Determinants Involved in Binding of Factor H and OspE-Targeting Antibodies Elicited during Borrelia burgdorferi Infection in Mice

机译:参与小鼠伯氏疏螺旋体感染期间H因子和与OspE靶向抗体结合的OspE决定簇的分析

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Immune evasion by Lyme spirochetes is a multifactorial process involving numerous mechanisms. The OspE protein family undergoes antigenic variation during infection and binds factor H (fH) and possibly FHL-1/reconectin. In Borrelia burgdorferi B31MI, the OspE family consists of three paralogs: BBL39 (ErpA), BBP38, and BBN38 (ErpP). BBL39 and BBP38 are identical and therefore are referred to here as BBL39. The goals of this study were to assess the specificity of the antibody (Ab) response to the OspE paralogs and to identify the domains or determinants of OspE that are required for the binding of fH and OspE-targeting Abs that develop during infection. Here we demonstrate that at least some of the anti-OspE Abs produced during infection are paralog specific and that Ab binding requires conformational determinants whose formation requires both the N- and C-terminal domains of OspE. The binding of fH to OspE was also found to be dependent on conformational determinants. It is also demonstrated here that all of the OspE paralogs expressed by B. burgdorferi B31MI are capable of binding fH. The binding of fH to members of the OspF protein family was also assessed. In contrast to an earlier report, no binding of BBO39 or BBR42 to human fH was detected. Lastly, a series of competitive binding enzyme-linked immunosorbent assay analyses, designed to determine if fH and infection serum Abs bind to the same sites on OspE, revealed that these ligands interact with different regions of OspE.
机译:莱姆螺旋体的免疫逃逸是一个涉及多种机制的多因素过程。 OspE蛋白家族在感染过程中发生抗原变异,并与H因子(fH)以及FHL-1 / reconectin结合。在 B31MI中,OspE家族由三个旁系同源物组成:BBL39(ErpA),BBP38和BBN38(ErpP)。 BBL39和BBP38是相同的,因此在此称为BBL39。这项研究的目的是评估针对OspE旁系同源物的抗体(Ab)的特异性,并确定结合fH和感染过程中形成的靶向OspE的Abs所需的OspE的域或决定簇。在这里,我们证明了在感染过程中产生的至少一些抗OspE Ab具有同源物特异性,并且Ab结合需要构象决定簇,其形成需要OspE的N和C端域。还发现fH与OspE的结合取决于构象决定簇。这里还证明了 B表示的所有OspE旁系同源物。 burgdorferi B31MI能够结合fH。还评估了fH与OspF蛋白家族成员的结合。与先前的报告相反,未检测到BBO39或BBR42与人fH的结合。最后,旨在确定fH和感染血清Abs是否结合到OspE上相同位点的一系列竞争性结合酶联免疫吸附分析表明,这些配体与OspE的不同区域相互作用。

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