[Report] Pathogenic CD4 T cells in type 1 diabetes recognize epitopes formed by peptide fusion
T cell–mediated destruction of insulin-producing β cells in the pancreas causes type 1 diabetes (T1D). CD4 T cell responses play a central role in β cell destruction, but the identity of the epitopes recognized by pathogenic CD4 T cells remains unknown. We found that diabetes-inducing CD4 T cell clones isolated from nonobese diabetic mice recognize epitopes formed by covalent cross-linking of proinsulin peptides to other peptides present in β cell secretory granules. These hybrid insulin peptides (HIPs) are antigenic for CD4 T cells and can be detected by mass spectrometry in β cells. CD4 T cells from the residual pancreatic islets of two organ donors who had T1D also recognize HIPs. Autoreactive T cells targeting hybrid peptides may explain how immune tolerance is broken in T1D. Authors: Thomas Delong, Timothy A. Wiles, Rocky L. Baker, Brenda Bradley, Gene Barbour, Richard Reisdorph, Michael Armstrong, Roger L. Powell, Nichole Reisdorph, Nitesh Kumar, Colleen...