{"title":"Epitope Hierarchy in Type 1 Diabetes Pathogenesis.","authors":"Thomas Delong, Maki Nakayama","doi":"10.1101/cshperspect.a041594","DOIUrl":null,"url":null,"abstract":"<p><p>Type 1 diabetes (T1D) is an autoimmune disease mediated by T cells destroying insulin-producing β cells. Identifying the antigenic epitopes targeted by autoreactive T cells is crucial for understanding pathogenesis, detecting biomarkers, and developing immunotherapies. This paper covers T-cell epitopes in T1D, focusing on pre-proinsulin and hybrid insulin peptides (HIPs) as major autoantigens. Substantial evidence highlights epitopes in the insulin B-chain and C-peptide as dominant targets for pathogenic CD4 and CD8 T cells infiltrating the islets. HIPs, formed by proinsulin fragments ligated to other peptides, constitute a novel class of epitopes detected in human and mouse islets. In addition, the paper also examines neoepitopes arising from posttranslational modifications, splice variants, and defective ribosomal products. A key challenge is differentiating genuinely pathogenic epitopes driving disease from nonpathogenic mimotopes. Identifying any essential, indispensable epitopes among this array could enable the development of antigen-specific immunotherapies targeting the root causative factors underlying T1D.</p>","PeriodicalId":10452,"journal":{"name":"Cold Spring Harbor perspectives in medicine","volume":" ","pages":""},"PeriodicalIF":7.8000,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cold Spring Harbor perspectives in medicine","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1101/cshperspect.a041594","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"MEDICINE, RESEARCH & EXPERIMENTAL","Score":null,"Total":0}
引用次数: 0
Abstract
Type 1 diabetes (T1D) is an autoimmune disease mediated by T cells destroying insulin-producing β cells. Identifying the antigenic epitopes targeted by autoreactive T cells is crucial for understanding pathogenesis, detecting biomarkers, and developing immunotherapies. This paper covers T-cell epitopes in T1D, focusing on pre-proinsulin and hybrid insulin peptides (HIPs) as major autoantigens. Substantial evidence highlights epitopes in the insulin B-chain and C-peptide as dominant targets for pathogenic CD4 and CD8 T cells infiltrating the islets. HIPs, formed by proinsulin fragments ligated to other peptides, constitute a novel class of epitopes detected in human and mouse islets. In addition, the paper also examines neoepitopes arising from posttranslational modifications, splice variants, and defective ribosomal products. A key challenge is differentiating genuinely pathogenic epitopes driving disease from nonpathogenic mimotopes. Identifying any essential, indispensable epitopes among this array could enable the development of antigen-specific immunotherapies targeting the root causative factors underlying T1D.
1 型糖尿病(T1D)是一种由 T 细胞破坏产生胰岛素的 β 细胞介导的自身免疫性疾病。确定自反应 T 细胞靶向的抗原表位对于了解发病机制、检测生物标记物和开发免疫疗法至关重要。本文介绍了 T1D 中的 T 细胞表位,重点是作为主要自身抗原的前胰岛素和混合胰岛素肽(HIPs)。大量证据表明,胰岛素 B 链和 C 肽中的表位是浸润胰岛的致病性 CD4 和 CD8 T 细胞的主要目标。由原胰岛素片段与其他肽连接而成的HIPs是在人类和小鼠胰岛中检测到的一类新型表位。此外,论文还研究了翻译后修饰、剪接变体和核糖体缺陷产物产生的新表位。一个关键的挑战是区分真正致病的表位与非致病的拟态表位。在这一系列表位中找出任何基本的、不可或缺的表位,就能开发出针对T1D根本致病因素的抗原特异性免疫疗法。
期刊介绍:
Cold Spring Harbor Perspectives in Medicine is a monthly online publication comprising reviews on different aspects of a variety of diseases, covering everything from the molecular and cellular bases of disease to translational medicine and new therapeutic strategies.
Cold Spring Harbor Perspectives in Medicine is thus unmatched in its depth of coverage and represents an essential source where readers can find informed surveys and critical discussion of advances in molecular medicine.