Trigger For T1DM: A Research Map
Scientists have identified the possible trigger for type 1 diabetes mellitus (T1DM).
The T cells of the immune system do not recognise self-antigens, i.e., the body’s own cells. Therefore, they are protected from the attack of the immune system. In T1DM and other autoimmune disorders, this protective system gets disrupted1.
Dr Delong and his colleagues carried out an experiment to study the trigger in T1DM. They isolated T cells from a T1DM mouse model and determined the trigger that is recognised as a foreign body in the insulin-producing β-cells. They recognised a modified version of insulin which acted as an antigen. They also observed that the immune T cells from pancreatic islets of two organ donors with T1DM recognised hybrid insulin peptides (HIPs). This study concluded that these HIPs may have a significant role as a trigger to the immune system and hence attack the body’s insulin-producing pancreatic β-cells, and thus causing T1DM1. Antibodies from the blood of T1DM patients recognised the HIPs in the mouse. This suggests that a human equivalent may also exist.
Insulin is considered to be an important autoantigen for β-cell in T1DM. However, according to a recent discovery, two more secretory granule proteins, islet amyloid polypeptide (IAPP) and chromogranin A (Chg A), are also considered to be the source of antigenic peptides in T1DM2.
HIPs act as key antigens for the autoreactive T cells and causes loss of self-tolerance in human T1DM. They may also form in the other endocrine tissues and could be a trigger for self-antigens in the other autoimmune disorders.
- Delong T, et al. Pathogenic CD4T cells in type 1 diabetes recognize epitopes formed by peptide fusion. Science. 2017;351(6274): 676-678.
- Haskins, Kathryn M. Hybrid Peptides as Autoantigens for Diabetogenic CD4T Cells. National Institutes of Health. (http://grantome.com/grant/NIH/R01-DK081166-06A1).