Understanding Autoimmune Diabetes through the Prism of the Tri-Molecular Complex

• Published in: Frontiers in endocrinology (Lausanne) Vol. 8; p. 351
• Main Authors: Bettini, Matthew L, Bettini, Maria
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Media S.A 14.12.2017
• Subjects: autoimmunity; Endocrinology; human leukocyte antigen; regulatory T cell; T cell; thymic selection; type 1 diabetes; thymic selection; type 1 diabetes; regulatory T cell; autoimmunity; human leukocyte antigen; T cell
• ISSN: 1664-2392; 1664-2392
• DOI: 10.3389/fendo.2017.00351

The strongest susceptibility allele for Type 1 Diabetes (T1D) is human leukocyte antigen (HLA), which supports a central role for T cells as the drivers of autoimmunity. However, the precise mechanisms that allow thymic escape and peripheral activation of beta cell antigen-specific T cells are still largely unknown. Studies performed with the non-obese diabetic (NOD) mouse have challenged several immunological dogmas, and have made the NOD mouse a key experimental system to study the steps of immunodysregulation that lead to autoimmune diabetes. The structural similarities between the NOD I-A and HLA-DQ8 have revealed the stability of the T cell receptor (TCR)/HLA/peptide tri-molecular complex as an important parameter in the development of autoimmune T cells, as well as afforded insights into the key antigens targeted in T1D. In this review, we will provide a summary of the current understanding with regard to autoimmune T cell development, the significance of the antigens targeted in T1D, and the relationship between TCR affinity and immune regulation.