Identification of novel HLA-A0201-restricted T-cell epitopes against thyroid antigens in autoimmune thyroid diseases
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ORIGINAL ARTICLE
Identification of novel HLA-A0201-restricted T-cell epitopes against thyroid antigens in autoimmune thyroid diseases Yun Cai1 Xinyu Xu1 Zheng Zhang2 Ping Wang3 Qingfang Hu1 Yu Jin1 Zhixiao Wang1 Xiaoyun Liu1 Tao Yang1 ●
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Received: 23 December 2019 / Accepted: 6 March 2020 © Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract 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. Keywords T-cell AITD Epitope Autoimmunity ●
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These authors contributed equally: Yun Cai, Xinyu Xu Supplementary information The online version of this article (https:// doi.org/10.1007/s12020-020-02264-x) contains supplementary material, which is available to authorized users. * Tao Yang [email protected] 1
Department of Endocrinology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, China
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Department of Critical Care Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing Jiangsu Province, China
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Department of Endocrinology, The Second Hospital of Nanjing, Nanjing University of Chinese Medicine, Nanjing Jiangsu Province, China
Introduction Autoimmune thyroid diseases (AITD), broadly including Graves’ dise
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