Neoepitopes: a new take on beta cell autoimmunity in type 1 diabetes
Type 1 diabetes is an autoimmune disease caused by T cell-mediated destruction of pancreatic insulin-producing beta cells. The epitopes recognised by pathogenic T cells in human type 1 diabetes are poorly defined; however, a growing body of evidence suggests that T cell responses against neoepitopes contribute to beta cell destruction in type 1 diabetes. Neoepitopes are formed when self-proteins undergo post-translational modification to create a new epitope that is recognised by T- or B cells. Here we review the role of human T cell responses against neoepitopes in the immune pathogenesis of type 1 diabetes. Specifically, we review the different approaches to identifying neoepitopes relevant to human type 1 diabetes and outline several advances in this field that have occurred over the past few years. We also discuss the application of neoepitopes to the development of antigen-specific therapies for type 1 diabetes and the unresolved challenges that need to be overcome before the full repertoire of neoepitopes recognised by pathogenic human T cells in type 1 diabetes can be determined. This information may then be used to develop antigen-specific therapies for type 1 diabetes and assays to monitor changes in pathogenic, beta cell-specific T cell responses.
KeywordsAntigen-specific therapy Beta cells Hybrid insulin peptides Neoepitopes Post-translational modification Review T cells Type 1 diabetes
Hybrid insulin peptides
Islet amyloid polypeptide
T cell receptor
All authors were responsible for drafting the article and revising it critically for important intellectual content. All authors approved the version to be published.
Work in the authors’ laboratory is supported by: JDRF [JDRF 5-CDA-2014-210-A-N] (SM); The National Health and Medical Research Council (NHMRC GNT123586) (SM); Diabetes Australia Research Trust Millennium Award (Y17M1-MANS) (SM); Diabetes Australia Research Program (Y18G-ELSC) (CE); and the Operational Infrastructure Support Program of the Victorian Government (SM, AD and CE). The authors have no financial conflicts to declare.
Duality of interest
The authors declare that there is no duality of interest associated with this manuscript.
- 26.Strollo R, Vinci C, Napoli N, Pozzilli P, Ludvigsson J, Nissim A (2017) Antibodies to post-translationally modified insulin as a novel biomarker for prediction of type 1 diabetes in children. Diabetologia 60(8):1467–1474. https://doi.org/10.1007/s00125-017-4296-1 CrossRefPubMedPubMedCentralGoogle Scholar
- 36.Koch R (1882) Die Aetiologie der Tuberculose. Berl Klin Wscht 19:221 [article in German]Google Scholar