Type 1 diabetes is the autoimmune form of diabetes, in which insulin-producing beta cells in the pancreas are destroyed by immune cells, especially those known as T cells. Insulin is the hormone that regulates levels of glucose in the blood and without insulin, a life-threatening disease results. Currently, there is no cure for type 1 diabetes. Now, a study led by researchers at the University of Colorado has identified a new class of antigens that may be a contributing factor to type 1 diabetes.
Previous studies show antigens for T cells are pieces of proteins, or protein fragments (peptides) that have to be taken up and presented to the T cells by antigen-presenting cells. Normally, a CD4 T cell is supposed to respond to foreign antigens, like a viral peptide. However, in autoimmune disease the T cells respond to antigens that are generated in the body; such proteins and peptides are called autoantigens. When an autoreactive T cell sees its antigen, it becomes activated and can initiate disease. It has been hypothesized that by identifying those antigens, the global medical community may be able to use that information to detect autoreactive T cells early in disease, or better yet, in at-risk individuals. If they are able to use the antigens to turn off destructive T cells, they may be able to prevent the disease. The current study focused on autoreactive CD4 T cells using a mouse model of autoimmune diabetes with view to identifying the antigens that activate these T cells.
The current study analyzed the fractions of beta cells that contain antigen for autoreactive CD4 T cells in order to identify autoantigens in type 1 diabetes. Results identify a new class of antigens that consist of insulin fragments fused to peptides of other proteins present in beta cells. Data findings show that fusion leads to generation of hybrid insulin peptides that are not encoded in an individual’s genome.
The team surmise that if peptides in the body are modified from their original form, they essentially become ‘foreign’ to the immune system and this may explain why they become targets for the autoreactive T cells. They go on to add that the discovery of hybrid peptides as targets of the immune system provides a plausible explanation of how the immune system is tricked into destroying the body’s own beta cells. For the future, the researchers state that the discovery may also lead to a better understanding of other autoimmune diseases.