Identification of novel HLA-A0201-restricted T-cell epitopes against thyroid antigens in autoimmune thyroid diseases
Identification of novel HLA-A0201-restricted T-cell epitopes against thyroid antigens in autoimmune thyroid diseases
复制标题
DOI：
10.1007/s12020-020-02264-x
复制
发表时间：
2020-03-20
期刊：
影响因子：
3.7
通讯作者：
Yang, Tao
中科院分区：
文献类型：
--
作者：
Cai, Yun;Xu, Xinyu;Yang, Tao
目的桥本甲状腺炎（HT）和Graves病（GD）引起自身免疫性甲状腺炎的不同机制尚不清楚。本研究的目的是识别甲状腺抗原特异性CD 8 + T细胞表位，并探讨这些表位与甲状腺自身抗体、病程和分型在这两种疾病中的关系。方法采用免疫荧光法测定血清游离硫碘甲状腺原氨酸、游离四碘甲状腺原氨酸、促甲状腺激素、TgAb、TPOAb，放射免疫法测定TRAb。应用HLA I类肽亲和力算法预测对HLA-A*0201盲的候选甲状腺自身抗原肽。ELISpot测定用于检测Tg-、TPO-和TSHR-特异性CD 8 + T细胞。结果TG-6为GD患者HLA-A*0201限制性CTL表位。TG-6、TG-7、TG-10、TG-11和TPO-6在GD患者中为免疫显性，而HT患者为免疫显性（TG-6：38.5 vs. 8%，P = 0.034; TG-7、TG-10、TG-11和TPO-6：23.1 vs. 0%，P = 0.034）。GD组TG-6阳性率为35.8%，高于健康对照组（0%）（P = 0.011），但HT组TG-6阳性率与健康对照组比较差异无统计学意义。亚组分析显示TgAb阴性HT患者的T细胞对TG-6的反应性更强（0 vs. 40%，P = 0.033）。HT和GD患者TPOAb、TRAb、用药与病程无相关性。结论我们首次报道了HT和GD这两种疾病识别不同的抗原特异性CD 8阳性T细胞。Tg可能是GD患者甲状腺自身抗原破坏耐受的主要原因。它可以提高我们对自身免疫性甲状腺疾病发病机制的认识，并在肽疫苗治疗方面提供新的治疗工具。
Purpose The different mechanisms that trigger the autoimmune attack to the thyroid between Hashimoto's thyroiditis (HT) and Graves' disease (GD) are still unclear. The aim of this study was to recognize thyroid antigens specific CD8+ T-cell epitopes and explore the relationship between these epitopes and thyroid autoantibodies, duration and classification in these two diseases. Methods Free thiiodothyronine, free tetraiodothyronine, thyroid-stimulating hormone, TgAb, and TPOAb were all measured by immunochemiluminometric assays, while TRAb was tested by radioimmunoassay. HLA class I peptide affinity algorithms were applied to predict candidate thyroid autoantigen peptides that blind to HLA-A*0201. The ELISpot assay was used to detect Tg-, TPO-, and TSHR-specific CD8+ T cells. Results We demonstrated that TG-6 was a novel HLA-A*0201-restricted CTL epitope in GD. TG-6, TG-7, TG-10, TG-11, and TPO-6 were immunodominant in GD patients compared with HT patients (TG-6: 38.5 vs. 8%, P = 0.034; TG-7, TG-10, TG-11, and TPO-6: 23.1 vs. 0%, P = 0.034). The immunodominance of TG-6 in GD patients was more evident than healthy controls (HC) (TG-6: 35.8 vs. 0%, P = 0.011), but there was no statistically significant difference between HT patients and HC. Subgroup analyses revealed the T-cell responsiveness to TG-6 was stronger in TgAb-negative HT patients (0 vs. 40%, P = 0.033). However, there was no correlation showed for TPOAb, TRAb, medication and duration in both HT and GD patients. Conclusions We report for the first time that both diseases, HT and GD, recognize different antigen-specific CD8-positive T cells. Tg maybe the dominant thyroid autoantigen contributing to breaking tolerance in GD. It could improve our knowledge of autoimmune thyroid diseases pathogenesis as well as offer new therapeutical tools in terms of peptide vaccine therapy.