Non-Genetically Encoded Epitopes Are Relevant Targets in Autoimmune Diabetes.
Non-Genetically Encoded Epitopes Are Relevant Targets in Autoimmune Diabetes.
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DOI：
10.3390/biomedicines9020202
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发表时间：
2021-02-17
期刊：
影响因子：
4.7
通讯作者：
James EA
中科院分区：
文献类型：
--
作者：
Nguyen H;Guyer P;Ettinger RA;James EA
胰岛抗原反应性 T 细胞在促进 1 型糖尿病 (T1D) β 细胞破坏中发挥关键作用。自身反应性 T 细胞通常通过胸腺中的负选择而被删除或偏离调节表型。然而，这些过程并不完美，即使是健康的个体也有潜在的自身反应性 T 细胞库。目前还不太清楚的是，胰岛素和其他 β 细胞特异性抗原的耐受性是如何丧失的。胰岛自身抗体是疾病风险的最佳预测因子，已知可识别胰岛素原、GAD65、IA-2 和 ZnT8 等经典抗原。这些抗体被认为是通过识别这些相同抗原靶标的自身反应性 CD4+ T 细胞的扩增来支持的。然而，最近的研究发现了新的非基因编码表位类别，它们可能反映了中枢和外周耐受性的关键差距。值得注意的是，其中一些特异性，包括来自酶促翻译后修饰的抗原和混合胰岛素肽的表位，在 T1D 患者的外周血中以相对较高的频率存在。我们的结论是，识别非基因编码表位的 CD4+ T 细胞可能对 T1D 胰岛自身免疫的进展做出重要贡献。我们进一步建议，这些类别的新表位应被视为诱导抗原特异性耐受策略的可能靶标。
Islet antigen reactive T cells play a key role in promoting beta cell destruction in type 1 diabetes (T1D). Self-reactive T cells are typically deleted through negative selection in the thymus or deviated to a regulatory phenotype. Nevertheless, those processes are imperfect such that even healthy individuals have a reservoir of potentially autoreactive T cells. What remains less clear is how tolerance is lost to insulin and other beta cell specific antigens. Islet autoantibodies, the best predictor of disease risk, are known to recognize classical antigens such as proinsulin, GAD65, IA-2, and ZnT8. These antibodies are thought to be supported by the expansion of autoreactive CD4+ T cells that recognize these same antigenic targets. However, recent studies have identified new classes of non-genetically encoded epitopes that may reflect crucial gaps in central and peripheral tolerance. Notably, some of these specificities, including epitopes from enzymatically post-translationally modified antigens and hybrid insulin peptides, are present at relatively high frequencies in the peripheral blood of patients with T1D. We conclude that CD4+ T cells that recognize non-genetically encoded epitopes are likely to make an important contribution to the progression of islet autoimmunity in T1D. We further propose that these classes of neo-epitopes should be considered as possible targets for strategies to induce antigen specific tolerance.
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DOI：
10.1126/science.aad2791
发表时间：
2016-02-12
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
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Haskins K
影响因子：
82.9
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影响因子：
64.8
作者：
Clemente-Casares, Xavier;Blanco, Jesus;Santamaria, Pere
通讯作者：
Santamaria, Pere
影响因子：
6.8
作者：
Dodson, G;Steiner, D
通讯作者：
Steiner, D
影响因子：
30.5
作者：
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通讯作者：
Klein, L