Antigens that may trigger diabetes identified

Washington: Scientists have identified a new class of antigens that may be a contributing factor to type 1 diabetes. 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.

In autoimmune disease, the key question is why the immune system attacks the body's own tissues. 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. "Our lab studies the type of T cell known as a CD4 T cell. We have focused on autoreactive CD4 T cells using a mouse model of autoimmune diabetes," said Kathryn Haskins from University of Colorado in US.

"We have been especially interested in identifying the antigens that activate these T cells," said Haskins. 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.

But in autoimmune disease, the autoreactive CD4 T cells respond to peptides that are generated in the body. Such peptides are called autoantigens. When an autoreactive T cell sees its antigen, it becomes activated and can initiate disease. By identifying those antigens, scientists 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. Researchers conducted experiments to analyse the
fractions of beta cells that contain antigen for autoreactive CD4 T cells in order to identify autoantigens in type 1 diabetes.

They discovered a new class of antigens that consist of insulin fragments fused to peptides of other proteins present in beta cells. That fusion leads to generation of hybrid insulin peptides that are not encoded in an individual's genome.

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, researchers said.

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. The discovery may also lead to a better understanding of other autoimmune diseases.