N-terminal additions to the WE14 peptide of chromogranin A create strong autoantigen agonists in type 1 diabetes
Abstract
Type 1 diabetes is an autoimmune disease in which the insulin-producing beta cells within the islets of Langerhans of the pancreas are destroyed by T cell-mediated immune attack. The peptide epitopes derived from islet proteins that are targeted by CD4+ T cells have been difficult to determine. We show in the nonobese diabetic (NOD) mouse model of the disease that a peptide (WE14) derived from chromogranin A is likely posttranslationally modified to create a target epitope. We hypothesize that the modification is caused by transpeptidation in which other peptides are fused to the N terminus of WE14. We propose that, in autoimmunity, new epitopes created in the target organs can be attacked by T cells that are normally nonreactive to natural self-antigens.
- Publication:
-
Proceedings of the National Academy of Science
- Pub Date:
- October 2015
- DOI:
- 10.1073/pnas.1517862112
- Bibcode:
- 2015PNAS..11213318J