Neoepitopes: a new take on beta cell autoimmunity in type 1 diabetes

  • Stuart I. ManneringEmail author
  • Anthony R. Di Carluccio
  • Colleen M. Elso


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.


Antigen-specific therapy Beta cells Hybrid insulin peptides Neoepitopes Post-translational modification Review T cells Type 1 diabetes 



Glucose-regulated protein


Hybrid insulin peptides


Islet amyloid polypeptide


T cell receptor


Contribution statement

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.


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Immunology and Diabetes UnitSt. Vincent’s Institute of Medical ResearchFitzroy, MelbourneAustralia
  2. 2.Department of MedicineUniversity of MelbourneFitzroy, MelbourneAustralia

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