Antigen recognition in type I diabetes

Type 1 diabetes (T1D) is the result of the autoimmune attack of autoantigen specific CD8+ and CD4+ T-cells against the pancreatic beta cells, resulting in a deficit of insulin secretion with unwanted metabolic consequences. The aim of this proposal is to investigate the structural differences between T-cell receptors (TCRs) involved in T1D, focusing on their interaction with the different autoantigen:MHC complexes. We want to compare the structural features of three diabetogenic TCRs, bearing alpha chains 17.4, 17.5 and 17.6, which recognize the IGRP206-214 peptide in the context of the MHC class I molecule H2-Kd. This will help us understand how the change of few amino acids can impact TCRs avidity and the progression of T1D. Additionally, we have identified the 4.1 TCR, a highly diabetogenic receptor that can act as an anti- or pro-diabetogenic molecule depending on the MHC class II molecule it interacts with. We want to explore these interactions with the goal of identifying structu