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首页> 外文期刊>Clinical immunology: The official journal of the Clinical Immunology Society >Relationships between major epitopes of the IA-2 autoantigen in Type 1 diabetes: Implications for determinant spreading
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Relationships between major epitopes of the IA-2 autoantigen in Type 1 diabetes: Implications for determinant spreading

机译：1型糖尿病中IA-2自身抗原的主要表位之间的关系：对决定因素扩散的影响

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摘要

Diversification of autoimmunity to islet autoantigens is critical for progression to Type 1 diabetes. B-cells participate in diversification by modifying antigen processing, thereby influencing which peptides are presented to T-cells. In Type 1 diabetes, JM antibodies are associated with T-cell responses to PIP domain peptides. We investigated whether this is the consequence of close structural alignment ofJM and PTP domain determinants on IA-2. Fab fragments of IA-2 antibodies with epitopes mapped to the JM domain blocked IA-2 binding of antibodies that recognise epitopes in the IA-2 PTP domain. Peptides from both the JM and PTP domains were protected from degradation during proteolysis of JM antibody: IA-2 complexes and included those representing major T-cell determinants in Type 1 diabetes. The results demonstrate close structural relationships between JM and PTP domain epitopes on IA-2. Stabilisation of PTP domain peptides during proteolysis in JM-specific B-cells may explain determinant spreading in IA-2 autoimmunity. (C) 2015 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
机译：胰岛自身抗原的自身免疫多样化对于进展为1型糖尿病至关重要。 B细胞通过修饰抗原过程参与多样化，从而影响向T细胞呈递的肽。在1型糖尿病中，JM抗体与T细胞对PIP结构域肽的反应相关。我们调查这是否是IA-2上JM和PTP结构域决定簇紧密结构比对的结果。具有定位到JM域的表位的IA-2抗体的Fab片段阻断了识别IA-2 PTP域中的表位的抗体的IA-2结合。在JM抗体：IA-2复合物的蛋白水解过程中，可保护来自JM和PTP域的肽免于降解，包括代表1型糖尿病主要T细胞决定簇的肽。结果表明IA-2上的JM和PTP域表位之间紧密的结构关系。在JM特异性B细胞的蛋白水解过程中，PTP结构域肽的稳定可能解释了IA-2自身免疫中的决定因素扩散。 （C）2015作者。由Elsevier Inc.发行。这是CC BY许可（http://creativecommons.org/licenses/by/4.0/）下的开放访问文章。

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