Immunology and Diabetes Unit, St. Vincent's Institute of Medical Research, Melbourne, VIC, Australia.
Department of Medicine, University of Melbourne, St. Vincent's Hospital, Melbourne, VIC, Australia.
Front Immunol. 2021 Apr 30;12:667870. doi: 10.3389/fimmu.2021.667870. eCollection 2021.
In 2016 Delong et al. discovered a new type of neoepitope formed by the fusion of two unrelated peptide fragments. Remarkably these neoepitopes, called hybrid insulin peptides, or HIPs, are recognized by pathogenic CD4 T cells in the NOD mouse and human pancreatic islet-infiltrating T cells in people with type 1 diabetes. Current data implicates CD4 T-cell responses to HIPs in the immune pathogenesis of human T1D. Because of their role in the immune pathogenesis of human T1D it is important to identify new HIPs that are recognized by CD4 T cells in people at risk of, or with, T1D. A detailed knowledge of T1D-associated HIPs will allow HIPs to be used in assays to monitor changes in T cell mediated beta-cell autoimmunity. They will also provide new targets for antigen-specific therapies for T1D. However, because HIPs are formed by the fusion of two unrelated peptides there are an enormous number of potential HIPs which makes it technically challenging to identify them. Here we review the discovery of HIPs, how they form and discuss approaches to identifying new HIPs relevant to the immune pathogenesis of human type 1 diabetes.
2016 年，德龙等人发现了一种由两个不相关的肽片段融合形成的新型新表位。值得注意的是，这些新表位被称为杂交胰岛素肽（HIPs），可被 NOD 小鼠中的致病性 CD4 T 细胞以及 1 型糖尿病患者胰腺胰岛浸润 T 细胞识别。目前的数据表明，CD4 T 细胞对 HIPs 的反应与人类 T1D 的免疫发病机制有关。由于 HIPs 在人类 T1D 的免疫发病机制中的作用，因此识别处于 T1D 风险中或患有 T1D 的人群中被 CD4 T 细胞识别的新 HIPs 非常重要。对 T1D 相关 HIPs 的详细了解将允许 HIPs 用于检测 T 细胞介导的胰岛自身免疫变化的检测。它们还将为 T1D 的抗原特异性治疗提供新的靶点。但是，由于 HIPs 是由两个不相关的肽融合形成的，因此存在大量潜在的 HIPs，这使得识别它们在技术上具有挑战性。在这里，我们回顾了 HIPs 的发现，它们的形成方式，并讨论了识别与人类 1 型糖尿病免疫发病机制相关的新 HIPs 的方法。
