Characterization of immune response to novel HLA-A2-restricted epitopes from zinc transporter 8 in type 1 diabetes.
Characterization of immune response to novel HLA-A2-restricted epitopes from zinc transporter 8 in type 1 diabetes.
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DOI：
10.1016/j.vaccine.2015.10.108
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发表时间：
2016-02
期刊：
影响因子：
5.5
通讯作者：
Xinyu Xu;Yong Gu;Lingling Bian;Yun Shi;Yun Cai;Yang Chen;Heng Chen;L. Qian;Xiangmei Wu;Kuanfeng Xu;R. Mallone;H. Davidson;Liping Yu;Jinxiong She;Mei Zhang;Tao Yang
中科院分区：
文献类型：
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作者：
Xinyu Xu;Yong Gu;Lingling Bian;Yun Shi;Yun Cai;Yang Chen;Heng Chen;L. Qian;Xiangmei Wu;Kuanfeng Xu;R. Mallone;H. Davidson;Liping Yu;Jinxiong She;Mei Zhang;Tao Yang
最近有报道称，人类1型糖尿病（T1 D）中存在ZnT 8特异性CD 8 + T细胞，尽管不同实验室的结果不一致。方法采用计算机算法、T2细胞系MHC-肽结合和解离试验、HLA-A2转基因小鼠（Tg）鉴定和体内CTL试验等方法筛选ZnT 8的HLA-A2限制性T细胞候选肽。结果发现ZnT 8107 -116（115）、ZnT 8110 -118和ZnT 8177 - 186是T1 D患者HLA-A*0201限制性CTL表位。ZnT 8107 -116（115）、ZnT 8115 -123、ZnT 8153 -161、ZnT 8177 - 186和ZnT 8291 - 300代表T1 D的潜在主要生物标志物。针对这些表位的T细胞应答在最近诊断的患者和长期存在的患者之间显示出不同的分布。此外，他们表现出不同种族之间的歧视性表现。我们还比较了本文使用的表位鉴定策略的性能。T1 D patients. Conclusions T1 D个体自身免疫性T细胞应答的差异可能为T1 D的预测和预防开辟新的途径。它还为免疫干预提供了有效的策略。
ObjectiveZnT8-specific CD8+ T cells in human type 1 diabetes (T1D) have been reported recently, although the results from different laboratories are inconsistent. We aimed to characterize these ZnT8 specific CD8+ T cells and validate assays to screen peptide libraries.MethodsWe screened HLA-A2-restricted T cell candidate peptides of ZnT8 with different methods including computer algorithms, MHC-peptide binding and dissociation assays in T2 cell line, identification in HLA-A2 transgenic (Tg) mice andin vivoCTL assays. Then ELISpot assay was used to measure peptide-reactive T cell responses in 49 HLA-A2-restricted T1D patients.ResultsWe demonstrated that ZnT8107–116(115), ZnT8110–118, and ZnT8177–186were novel HLA-A*0201-restricted CTL epitopes in T1D patients. ZnT8107–116(115), ZnT8115–123, ZnT8153–161, ZnT8177–186and ZnT8291–300represent potentially major biomarkers for T1D. T cell responses against these epitopes showed different distributions between recently diagnosed and long-standing patients. Furthermore, they displayed discriminating performance among different ethnicities. We also compared the performance of the epitope identification strategies used herein. The epitopes which exhibited strong immunogenicity in HLA-A2 Tg mice were also well recognized by T1D patients.ConclusionsThe differences in autoimmune T cell responses among T1D individuals may open new avenues toward T1D prediction and prevention. It also provides efficient strategies for immune intervention.