T-Cell Epitopes and Neo-epitopes in Type 1 Diabetes: A Comprehensive Update and Reappraisal.

Abstract:

:The autoimmune disease type 1 diabetes is characterized by effector T-cell responses to pancreatic β-cell-derived peptides presented by HLA class I and class II molecules, leading ultimately to β-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 online supplementary material where 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.

journal_name

Diabetes

journal_title

Diabetes

authors

James EA,Mallone R,Kent SC,DiLorenzo TP

doi

10.2337/dbi19-0022

subject

Has Abstract

pub_date

2020-07-01 00:00:00

pages

1311-1335

issue

7

eissn

0012-1797

issn

1939-327X

pii

69/7/1311

journal_volume

69

pub_type

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