When an autoreactive T cell sees its antigen, it becomes activated and can initiate disease. (Representational image)
“Our lab studies the type of T cell known as a CD4 T cell,” said Kathryn Haskins from the University of Colorado School of Medicine in the US.
“We have focused on autoreactive CD4 T cells using a mouse model of autoimmune diabetes. We have been especially interested in identifying the antigens that activate these T cells,” Ms Haskins added in the paper published in journal Science.
Normally, a CD4 T cell is supposed to respond to “foreign” antigens. But 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. 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, the study finds.
Researchers conducted experiments to analyze 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.
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.