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T Cell Epitopes and Neo-epitopes in Type 1 Diabetes: A Comprehensive Update and Reappraisal
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posted on 2020-06-22, 17:10 authored by Ada AdminAda Admin, Eddie A. James, Roberto Mallone, Sally C. Kent, Teresa P. DiLorenzoThe 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 an online
appendix that cross-indexes 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 under-studied type 1 diabetes-associated HLA molecules.