SpeS: A Novel Superantigen and Its Potential as a Vaccine Adjuvant against Strangles
SpeS: A Novel Superantigen and Its Potential as a Vaccine Adjuvant against Strangles
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DOI：
10.3390/ijms21124467
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发表时间：
2020-06-01
影响因子：
5.6
通讯作者：
Waller, Andrew S.
中科院分区：
文献类型：
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作者：
Dominguez-Medina, C. Coral;Rash, Nicola L.;Waller, Andrew S.
细菌超抗原（sAgs）是免疫应答的强有力激活剂，其触发非特异性T细胞应答，伴随着促炎细胞因子的释放。马链球菌（Streptococcus zoovalmicus，S. equi）和动物链球菌（Streptococcus zoovalmicus，S.动物寄生虫（zoopellicus）产生在它们引起疾病的能力中起重要作用的sAg。窒息，由S.马传染病是世界范围内马最常见的传染病之一。在这里，我们报告的一个新的sAg的鉴定。动物模型，SpeS，并显示推定T细胞受体（TCR）结合基序突变（YAY至IAY）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。SpeS和SpeS（Y39 I）的融合为sixS。进行使用两种不同肽接头的马表面蛋白的免疫测定，以确定是否保持了MHCII类结合特性。增殖测定、qPCR和流式细胞术分析表明，与SpeS相比，SpeS（Y39 I）及其融合蛋白诱导更少的促有丝分裂活性和干扰素γ表达，同时保留抗原呈递细胞（APC）结合特性。我们的数据表明，SpeS（Y39 I）-表面蛋白融合可用于在体内将疫苗抗原导向抗原呈递细胞，具有增强抗原呈递和改善免疫应答的潜力。
Bacterial superantigens (sAgs) are powerful activators of the immune response that trigger unspecific T cell responses accompanied by the release of proinflammatory cytokines.Streptococcus equi(S. equi) andStreptococcus zooepidemicus(S. zooepidemicus) produce sAgs that play an important role in their ability to cause disease. Strangles, caused byS. equi, is one of the most common infectious diseases of horses worldwide. Here, we report the identification of a new sAg ofS. zooepidemicus, 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(Y39I)to sixS. equisurface 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(Y39I)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(Y39I)-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.