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
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