Type-1 Diabetes (T1D) is the major autoimmune disease affecting the juvenile population in which insulin-producing pancreatic β-cells are destroyed by self-reactive T-cells and B-cells. Emerging studies have identified the presence of autoantibodies and altered T-cell reactivity against several autoantigens in individuals who are at risk of developing T1D even before the clinical onset of diabetes. Whilst these findings could lead to the development of predictive biomarkers for early diagnosis, growing evidence on the generation of neoepitopes, epitope spreading and diverse antigen repertoire in T1D poses a major challenge for developing approaches to induce antigen-specific tolerance. Mechanisms of neoepitope generation include post-translational modifications of existing epitopes, aberrant translational products, peptide fusion, and differences in MHC binding registers. Here, we focus our discussion on how post-translational modifications can give rise to immunogenic neoepitopes in T1D and present our perspective on how it could affect the development of therapeutic approaches to induce antigen-specific tolerance.

1型糖尿病（T1D）是影响青少年人群的主要自身免疫疾病，在该人群中，产生胰岛素的胰腺β细胞被自身反应性T细胞和B细胞破坏。新兴研究已经发现，即使在糖尿病临床发作之前，也有可能发展为T1D的个体中存在自身抗体并改变了针对几种自身抗原的T细胞反应性。尽管这些发现可能会导致开发用于早期诊断的预测性生物标记物，但有关T1D中新表位，表位扩散和多种抗原库的证据不断增加，这对开发诱导抗原特异性耐受的方法构成了重大挑战。新表位产生的机制包括现有表位的翻译后修饰，异常翻译产物，肽融合，和MHC绑定寄存器的差异。在这里，我们集中讨论翻译后修饰如何在T1D中引起免疫原性新表位，并就其如何影响诱导抗原特异性耐受的治疗方法的发展提出我们的观点。