Abrogation of self-tolerance by misfolded self-antigens complexed with MHC class II molecules.
Abrogation of self-tolerance by misfolded self-antigens complexed with MHC class II molecules.
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DOI：
10.1126/sciadv.abj9867
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发表时间：
2022-03-04
期刊：
影响因子：
13.6
通讯作者：
Arase H
中科院分区：
文献类型：
--
作者：
Jin H;Kishida K;Arase N;Matsuoka S;Nakai W;Kohyama M;Suenaga T;Yamamoto K;Sasazuki T;Arase H
特定的 MHC II 类等位基因与各种自身免疫性疾病的易感性密切相关。尽管 MHC II 类分子的主要功能是将肽呈递给辅助 T 细胞，但 MHC II 类分子也可以像伴侣一样发挥作用，将错误折叠的细胞内蛋白质转运到细胞表面。在这项研究中，我们发现格雷夫斯病患者的自身抗体优先识别与格雷夫斯病风险等位基因的MHC II类分子复合的促甲状腺激素受体（TSHR），这表明由MHC II类分子转运的异常TSHR是格雷夫斯病产生的自身抗体的靶标。注射表达小鼠 TSHR 与 MHC II 类分子复合的细胞（但不单独注射 TSHR）的小鼠会产生抗 TSHR 自身抗体。这些发现表明，MHC II 类分子转运的异常自身抗原表现出与正常自身抗原不同的抗原特性，并消除了自身耐受性，为自身免疫提供了一种新的机制。 TSH 受体/MHC II 类复合物参与格雷夫斯病的发病机制。
Specific MHC class II alleles are strongly associated with susceptibility to various autoimmune diseases. Although the primary function of MHC class II molecules is to present peptides to helper T cells, MHC class II molecules also function like a chaperone to transport misfolded intracellular proteins to the cell surface. In this study, we found that autoantibodies in patients with Graves’ disease preferentially recognize thyroid-stimulating hormone receptor (TSHR) complexed with MHC class II molecules of Graves’ disease risk alleles, suggesting that the aberrant TSHR transported by MHC class II molecules is the target of autoantibodies produced in Graves’ disease. Mice injected with cells expressing mouse TSHR complexed with MHC class II molecules, but not TSHR alone, produced anti-TSHR autoantibodies. These findings suggested that aberrant self-antigens transported by MHC class II molecules exhibit antigenic properties that differ from normal self-antigens and abrogate self-tolerance, providing a novel mechanism for autoimmunity. The TSH receptor/MHC class II complex is involved in Graves’ disease pathogenesis.
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DOI：
10.1073/pnas.92.14.6567
发表时间：
1995-07-03
影响因子：
11.1
作者：
DAVENPORT, MP;QUINN, CL;HILL, AVS
通讯作者：
HILL, AVS
影响因子：
2
作者：
Kamijo, K;Ishikawa, K;Tanaka, M
通讯作者：
Tanaka, M
影响因子：
29.7
作者：
Blum JS;Wearsch PA;Cresswell P
通讯作者：
Cresswell P
DOI：
10.1007/978-1-62703-589-7_14
发表时间：
2013
期刊：
Methods in molecular biology (Clifton, N.J.)
影响因子：
--
作者：
Bozzacco, Leonia;Yu, Haiqiang
通讯作者：
Yu, Haiqiang
影响因子：
4.8
作者：
Kaneda, Toshio;Honda, Asako;Yoshida, Tadashi
通讯作者：
Yoshida, Tadashi