Researchers explain how immune tolerance could be broken in type 1 diabetes

Jack Woodfield
Mon, 15 Feb 2016
Researchers explain how immune tolerance could be broken in type 1 diabetes
A new class of antigens could be a contributing factor to type 1 diabetes, and also explain how immune tolerance is broken, according to new research.

Scientists at the University of Colorado School of Medicine believe that a T cell known as CD4 T cell could play a central role in the destruction of insulin-producing beta cells, which characterises type 1 diabetes.

A CD4 T cell usually responds to "foreign" antigens - these are substances that cause the body to evoke an immune response, such as bacteria or toxins - and fights off the threat.

However, in autoimmune diseases such as type 1 diabetes, T cells respond to antigens that are generated in the body. These are called autoantigens, and they cause T cells to become activated and initiate disease.

The researchers hope that by identifying the antigens that activate these T cells, they can detect them early in disease, or even among at-risk individuals. By manipulating autoantigens to deactivate destructive T cells, diseases such as type 1 diabetes could be prevented.

In this new study, the researchers isolated and examined CD4 T cell clones from a non-obese mouse model of autoimmune diabetes. They observed a new class of antigens located in the beta cells of the mice, which were analysed for autoreactive CD4 T cells.

These antigens consisted of insulin fragments fused to peptides or other proteins present in beta cells. When this fusion occurs, it results in the generation of hybrid insulin peptides (HIPs) that are not encoded in an individual's genome.

"These hybrid insulin peptides are antigenic for CD4 T cells," say the researchers, who then isolated the pancreatic islets of two individuals with type 1 diabetes. HIPs were recognised in both individuals, and the study team believe that HIPs could play an important role in driving disease.

If peptides in the body are modified from the original form, it could explain why they are targeted by autoreactive T cells. The peptides would be "foreign" to the immune system, and trick the body into destroying its own beta cells.

The Colorado School of Medicine team believe their findings could lead to a greater understanding of type 1 diabetes and other autoimmune disease.

The study was published in the online journal Science.
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