Title: The Structural Basis for a Transition State That Regulates Pore Formation in a Bacterial Toxin
Authors: Wade, KR
Lawrence, SL
Farrand, AJ
Hotze, EM
Kuiper, MJ
Gorman, MA
Christie, MP
Panjikar, S
Morton, CJ
Parker, MW
Tweten, RK
Issue Year: 2019
Publisher AMER SOC MICROBIOLOGY
Series MBIO:
Abstract 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.
URI: https://publications.svi.edu.au/publications/7882
Other Identifiers 10.1128/mBio.00538-19
Publication type Article