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Identification of novel HLA-A0201-restricted T-cell epitopes against thyroid antigens in autoimmune thyroid diseases

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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.

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Acknowledgements

This study was supported by grants from the National Natural Science Foundation of China (numbers 81530026, 81970707, and 81830023).

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  1. These authors contributed equally: Yun Cai, Xinyu Xu

Authors and Affiliations

  1. Department of Endocrinology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, China

    Yun Cai, Xinyu Xu, Qingfang Hu, Yu Jin, Zhixiao Wang, Xiaoyun Liu & Tao Yang

  2. Department of Critical Care Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, China

    Zheng Zhang

  3. Department of Endocrinology, The Second Hospital of Nanjing, Nanjing University of Chinese Medicine, Nanjing, Jiangsu Province, China

    Ping Wang

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  1. Yun Cai
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Cai, Y., Xu, X., Zhang, Z. et al. Identification of novel HLA-A0201-restricted T-cell epitopes against thyroid antigens in autoimmune thyroid diseases. Endocrine 69, 562–570 (2020). https://doi.org/10.1007/s12020-020-02264-x

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