T-Cell Epitopes and Neo-epitopes in Type 1 Diabetes: A Comprehensive Update and Reappraisal
T-Cell Epitopes and Neo-epitopes in Type 1 Diabetes: A Comprehensive Update and Reappraisal
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DOI：
10.2337/dbi19-0022
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发表时间：
2020-07-01
期刊：
影响因子：
7.7
通讯作者：
DiLorenzo, Teresa P.
中科院分区：
文献类型：
--
作者：
James, Eddie A.;Mallone, Roberto;DiLorenzo, Teresa P.
自身免疫性疾病 1 型糖尿病的特点是效应 T 细胞对 HLA I 类和 II 类分子呈递的胰腺 β 细胞衍生肽产生反应，最终导致 β 细胞死亡和胰岛素不足。尽管给定的 HLA 分子呈现大量肽，但只有那些被 T 细胞识别的肽才被指定为表位。鉴于 T 细胞表位与病因学的密切联系，T 细胞表位的发现和表征是 1 型糖尿病研究的一个重要方面。了解表位识别对于寻求抗原特异性免疫疗法和实施 T 细胞监测策略也至关重要。由于这些原因，针对 1 型糖尿病的 T 细胞表位的编目和评估在十多年前就完成了，为研究和临床界提供了重要的资源。在这里，我们对这项早期工作进行了急需的更新和重新评估，并包括在线交叉索引每个表位及其主要参考文献和免疫表位数据库（IEDB）标识符。我们的分析包括一个分级量表，用于对每个表位的可用证据程度进行评分，这传达了我们对表位评估的几个有用标准的看法。这项工作在对当前令人印象深刻的知识状况进行有效总结的同时，也暴露了一些缺陷。其中包括需要改进表位验证，因为很少有表位根据所采用的标准得分很高，并且缺乏对在几种正在研究的 1 型糖尿病相关 HLA 分子背景下识别的表位的研究。
The autoimmune disease type 1 diabetes is characterized by effector T-cell responses to pancreatic beta-cell-derived peptides presented by HLA class I and class II molecules, leading ultimately to beta-cell demise and insulin insufficiency. Although a given HLA molecule presents a vast array of peptides, only those recognized by T cells are designated as epitopes. Given their intimate link to etiology, the discovery and characterization of T-cell epitopes is a critical aspect of type 1 diabetes research. Understanding epitope recognition is also crucial for the pursuit of antigen-specific immunotherapies and implementation of strategies for T-cell monitoring. For these reasons, a cataloging and appraisal of the T-cell epitopes targeted in type 1 diabetes was completed over a decade ago, providing an important resource for both the research and the clinical communities. Here we present a much needed update and reappraisal of this earlier work and include onlinewhere we cross-index each epitope with its primary references and Immune Epitope Database (IEDB) identifier. Our analysis includes a grading scale to score the degree of evidence available for each epitope, which conveys our perspective on several useful criteria for epitope evaluation. While providing an efficient summary of the arguably impressive current state of knowledge, this work also brings to light several deficiencies. These include the need for improved epitope validation, as few epitopes score highly by the criteria employed, and the dearth of investigations of the epitopes recognized in the context of several understudied type 1 diabetes-associated HLA molecules.