State Key Laboratory of Toxicology and Medical Countermeasures, Institute of Pharmacology and Toxicology, 27 Taiping Road, Beijing, 100850, China; School of Medical Devices, Shenyang Pharmaceutical University, Shenyang, 117004, China.
State Key Laboratory of Toxicology and Medical Countermeasures, Institute of Pharmacology and Toxicology, 27 Taiping Road, Beijing, 100850, China.
Biochem Biophys Res Commun. 2021 Apr 16;549:120-127. doi: 10.1016/j.bbrc.2021.02.057. Epub 2021 Mar 2.
Staphylococcal enterotoxin B (SEB), one of the exotoxins produced by Staphylococcus aureus, is the key toxin that causes poisoning reactions and toxic shock syndrome. In the current research work, a novel human antibody named LXY8 was screened from a human phage display antibody library, and LXY8 blocked the interaction between SEB and the T cell receptor (TCR). The binding activity between LXY8 and SEB was 0.525 nM. Furthermore, LXY8 could effectively inhibit the SEB-induced activation of peripheral blood mononuclear cells and release of cytokines. In the BALB/c mouse model, LXY8 effectively neutralized SEB toxicity in vivo. Finally, based on computer-guided molecular modeling, we designed a series of SEB mutation sites; these sites facilitated the determination of the key residues (i.e.EFNN) of SEB recognized by LXY8. The research revealed that the EFNN residues of SEB are important for specific antibody-antigen recognition. The results may be helpful for the development of antibody-based therapy for SEB-induced toxic shock syndrome.
金黄色葡萄球菌肠毒素 B（SEB）是金黄色葡萄球菌产生的外毒素之一，是引起中毒反应和中毒性休克综合征的关键毒素。在当前的研究工作中，从噬菌体展示抗体文库中筛选出一种新型人抗体 LXY8，LXY8 可阻断 SEB 与 T 细胞受体（TCR）的相互作用。LXY8 与 SEB 的结合活性为 0.525 nM。此外，LXY8 可有效抑制 SEB 诱导的外周血单个核细胞激活和细胞因子释放。在 BALB/c 小鼠模型中，LXY8 可有效中和 SEB 的体内毒性。最后，基于计算机指导的分子建模，我们设计了一系列 SEB 突变位点；这些位点有助于确定 LXY8 识别的 SEB 的关键残基（即 EFNN）。该研究表明，SEB 的 EFNN 残基对于特定的抗体-抗原识别很重要。这些结果可能有助于开发基于抗体的 SEB 诱导中毒性休克综合征的治疗方法。
