Key Laboratory of Zoonosis, The Ministry of Education, Jilin University, Changchun, China.
PLoS One. 2011 Apr 20;6(4):e19112. doi: 10.1371/journal.pone.0019112.
Schistosomal parasites can establish parasitization in a human host for decades; evasion of host immunorecognition including surface masking by acquisition of host serum components is one of the strategies explored by the parasites. Parasite molecules anchored on the membrane are the main elements in the interaction. Sjc23, a member of the tetraspanin (TSP) family of Schistosoma japonicum, was previously found to be highly immunogenic and regarded as a vaccine candidate against schistosomiasis. However, studies indicated that immunization with Sjc23 generated rapid antibody responses which were less protective than that with other antigens. The biological function of this membrane-anchored molecule has not been defined after decades of vaccination studies.
In this study, we explored affinity pull-down and peptide competition assays to investigate the potential binding between Sjc23 molecule and human non-immune IgG. We determined that Sjc23 could bind human non-immune IgG and the binding was through the interaction of the large extra-cellular domain (LED) of Sjc23 (named Sjc23-LED) with the Fc domain of human IgG. Sjc23 had no affinity to other immunoglobulin types. Affinity precipitation (pull-down assay) in the presence of overlapping peptides further pinpointed to a 9-amino acid motif within Sjc23-LED that mediated the binding to human IgG.
S. japonicum parasites cloak themselves through interaction with human non-immune IgG, and a member of the tetraspanin family, Sjc23, mediated the acquisition of human IgG via the interaction of a motif of 9 amino acids with the Fc domain of the IgG molecule. The consequence of this interaction will likely benefit parasitism of S. japonicum by evasion of host immune recognition or immunoresponses. This is the first report that an epitope of schistosomal ligand and its immunoglobulin receptor are defined, which provides further evidence of immune evasion strategy adopted by S. japonicum.
血吸虫寄生虫可以在人类宿主中寄生数十年;逃避宿主免疫识别,包括通过获取宿主血清成分进行表面掩蔽,是寄生虫探索的策略之一。寄生虫分子锚定在膜上是相互作用的主要元素。Sjc23 是日本血吸虫四跨膜蛋白(TSP)家族的一员,以前被发现具有高度免疫原性,被认为是血吸虫病疫苗的候选物。然而,研究表明,用 Sjc23 免疫产生的抗体反应比用其他抗原产生的抗体反应更快,但保护作用更差。经过几十年的疫苗接种研究,这种膜锚定分子的生物学功能仍未得到定义。
在这项研究中,我们通过亲和下拉和肽竞争实验来研究 Sjc23 分子与人类非免疫 IgG 之间的潜在结合。我们发现 Sjc23 可以与人类非免疫 IgG 结合,这种结合是通过 Sjc23 的大细胞外结构域(LED)(称为 Sjc23-LED)与人类 IgG 的 Fc 结构域相互作用实现的。Sjc23 与其他免疫球蛋白类型没有亲和力。在重叠肽存在的情况下进行亲和沉淀(下拉实验),进一步确定了 Sjc23-LED 内的一个 9 个氨基酸基序介导了与人类 IgG 的结合。
日本血吸虫寄生虫通过与人类非免疫 IgG 相互作用来伪装自己,四跨膜蛋白家族的一个成员 Sjc23 通过与 IgG 分子的 Fc 结构域相互作用的 9 个氨基酸基序来介导对人类 IgG 的获取。这种相互作用的结果可能有利于日本血吸虫逃避宿主免疫识别或免疫反应,从而有利于寄生虫的寄生。这是首次报道日本血吸虫配体的一个表位及其免疫球蛋白受体被定义,这为日本血吸虫采用的免疫逃避策略提供了进一步的证据。