Altered Peptides as Potential Antigens in Causing T1D

Chromogranin A is a protein produced by beta cells that has recently been implicated as a potential autoantigen in T1D. In a mouse model of autoimmune diabetes, a part of chromogranin A has been shown to be targeted by a series of specific T cells. When treated with an enzyme that has been linked to celiac disease, chromogranin A becomes more antigenic. Spontaneous protein changes are known to occur in other autoimmune diseases, and a similar process might trigger T1D. In this study, Dr. Haskins and her colleagues show that such a process is at least feasible in a mouse model of autoimmune diabetes. Preliminary work from Dr. Haskinss group also shows that this process may be relevant in humans as well.


Delong T, Baker RL, He J, Barbour G, Bradley B, Haskins K. Diabetes. 2012 Aug 21. [Epub ahead of print] Diabetogenic T-Cell Clones Recognize an Altered Peptide of Chromogranin A.

Investigators and Institutions:

This study was led by Dr. Katie Haskins at the University of Colorado at Denver School of Medicine and National Jewish Health.

Ramifications for Individuals with Type 1 Diabetes:

In T1D and other autoimmune diseases, the body mistakenly mounts an immune response to normal or native body components and these targets are known as antigens. The mechanisms by which this occurs in T1D are complex and not very well understood. One possibility is that modifications of the antigens might play a role. After undergoing these modifications, the altered components look different to the immune system than the unmodified or normal components. The immune system then recognizes the modified protein as foreign and mistakenly mounts an immune response to similar native components. In this research, Dr. Haskins concludes that modified antigens do occur in a mouse model of autoimmune diabetes. If this can translate to human disease, understanding their role in disease progression could lead to better therapeutics and biomarkers for T1D.

JDRF Involvement:

This study was funded through a grant to Dr. Katie Haskins and a post-doctoral fellowship to Dr. Thomas Delong.