The Use of Proteomics to Dissect the Molecular Specificities of T Cells in Type 1 Diabetes

Abstract

Presentation of peptides derived from beta cell proteins to autoreactive lymphocytes is critical for the development and progression of type 1 diabetes. How tolerance to beta cell antigens is broken is yet to be fully elucidated. The high metabolic demand on beta cells, the high concentration of granule proteins and the susceptibility of islets to cellular stress may all contribute to the presentation of abnormal ligands in the pancreas. Evidence for nonconventional presentation of peptide ligands and post-translational modification of peptides to T cells has emerged in both human studies and animal models of diabetes. Challenges in identifying targets of autoimmunity are being increasingly met by advances in modern mass spectrometry. Here we review recent advances in mass spectrometry and their application to studies of peptides involved in immune recognition in diabetes.