Animal Health Trust, Lanwades Park, Kentford, Newmarket CB8 7UU, UK.
Public Health England, 61 Colindale Avenue, London NW9 5EQ, UK.
Int J Mol Sci. 2020 Jun 23;21(12):4467. doi: 10.3390/ijms21124467.
Bacterial superantigens (sAgs) are powerful activators of the immune response that trigger unspecific T cell responses accompanied by the release of proinflammatory cytokines. () and () produce sAgs that play an important role in their ability to cause disease. Strangles, caused by , is one of the most common infectious diseases of horses worldwide. Here, we report the identification of a new sAg of , SpeS, and show that mutation of the putative T cell receptor (TCR)-binding motif (YAY to IAY) abrogated TCR-binding, whilst maintaining interaction with major histocompatibility complex (MHC) class II molecules. The fusion of SpeS and SpeS to six surface proteins using two different peptide linkers was conducted to determine if MHC class II-binding properties were maintained. Proliferation assays, qPCR and flow cytometry analysis showed that SpeS and its fusion proteins induced less mitogenic activity and interferon gamma expression when compared to SpeS, whilst retaining Antigen-Presenting Cell (APC)-binding properties. Our data suggest that SpeS-surface protein fusions could be used to direct vaccine antigens towards antigen-presenting cells in vivo with the potential to enhance antigen presentation and improve immune responses.
细菌超抗原(sAg)是一种强大的免疫激活剂,可引发非特异性 T 细胞反应,并伴有促炎细胞因子的释放。()和()产生的 sAg 在其致病能力中起着重要作用。由()引起的鼻疽是世界范围内马最常见的传染病之一。在这里,我们报告了()的一种新的 sAg,SpeS 的鉴定,并表明假定的 T 细胞受体(TCR)结合基序(YAY 到 IAY)的突变消除了 TCR 结合,同时保持与主要组织相容性复合体(MHC)Ⅱ类分子的相互作用。使用两种不同的肽接头将 SpeS 和 SpeS 融合到六个表面蛋白中,以确定 MHC Ⅱ类结合特性是否得到维持。增殖试验、qPCR 和流式细胞术分析表明,与 SpeS 相比,SpeS 和其融合蛋白诱导的有丝分裂活性和干扰素 γ表达较少,同时保留抗原呈递细胞(APC)结合特性。我们的数据表明,SpeS-表面蛋白融合物可用于在体内将疫苗抗原靶向抗原呈递细胞,具有增强抗原呈递和改善免疫反应的潜力。