Institute of Immunology, Third Military University, Chongqing, People's Republic of China.
Gynecol Endocrinol. 2009 Dec;25(12):828-38. doi: 10.3109/09513590903015536.
The follicle stimulating hormone (FSH) is of great importance in reproduction modulation of both sexes. The extracellular domain (ECD) of its receptor (FSHR) is crucial for FSH binding and subsequent signal transduction; therefore, it is the potential target for fertility control. To avoid unwanted side-effect when used as immunocontraceptive agent, the ECD was analysed by online prediction combined with molecular docking to identify the candidate B-cell epitopes. Four potential B-cell epitopes were identified and synthesised in tandem with Pan DR epitope. Then the epitope-based peptides were used to boost adult male mice following rhFSHR protein priming, thus to determine their immune responses and fertility inhibition capacity. Three of the four peptides showed suppressed fertility accompanied with small testis and lower serum testosterone level, which was consistent with absolutely lower sperm quantity and poor quality. Among the four epitope peptides, Pep2 displayed the lowest fertility rate of 26.67%, which was similar to that of rhFSHR homologously prime/boost mice (23.30 and 25.00%). Thus, we identified a novel immunodominant B-cell epitope by molecular docking and protein prime/peptide boost strategy.
卵泡刺激素（FSH）在两性生殖调控中具有重要作用。其受体（FSHR）的细胞外结构域（ECD）对于 FSH 结合和随后的信号转导至关重要；因此，它是生育控制的潜在靶点。为了避免作为免疫避孕药具使用时出现不良反应，通过在线预测结合分子对接分析了 ECD，以确定候选 B 细胞表位。鉴定了四个潜在的 B 细胞表位，并与 Pan DR 表位串联合成。然后，基于表位的肽在 rhFSHR 蛋白引发后用于增强成年雄性小鼠，从而确定它们的免疫反应和生育抑制能力。这四个肽中的三个显示出生育力降低，伴随着睾丸缩小和血清睾酮水平降低，这与精子数量绝对减少和质量差相一致。在这四个表位肽中，Pep2 显示出最低的生育率为 26.67%，与 rhFSHR 同源引发/增强小鼠（23.30%和 25.00%）相似。因此，我们通过分子对接和蛋白引发/肽增强策略鉴定了一种新的免疫显性 B 细胞表位。
