| Title: | Pathogenic CD4 T cells in type 1 diabetes recognize epitopes formed by peptide fusion |
| Authors: | Delong, T Wiles, TA Baker, RL Bradley, B Barbour, G Reisdorph, R Armstrong, M Powell, RL Reisdorph, N Kumar, N Elso, CM DeNicola, M Bottino, R Powers, AC Harlan, DM Kent, SC Mannering, SI Haskins, K |
| Issue Year: | 2016 |
| Publisher | AMER ASSOC ADVANCEMENT SCIENCE |
| Series | Science: |
| Abstract | T cell-mediated destruction of insulin-producing beta cells in the pancreas causes type 1 diabetes T1D). CD4 T cell responses play a central role in beta 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 beta cell secretory granules. These hybrid insulin peptides HIPs) are antigenic for CD4 T cells and can be detected by mass spectrometry in beta 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. |
| URI: | https://publications.svi.edu.au/publications/2025 |
| Other Identifiers | 10.1126/science.aad2791 |
| Publication type | Article |
| Grant ID | GNT1061961 |