| Autoimmune disease is a growing health concern. Although much research has been focused on identifying the causes of autoimmune diseases, the mechanism still remains enigmatic. In this thesis I explore the hypothesis that somatic mutations play a role in the development of autoimmunity. I tested this hypothesis by determining whether human T cells could respond to pairs of self peptides (non-mutated germ line peptides) and mutated peptides (differing from self by one amino acid due to mitochondrial DNA somatic mutations) from mitochondrial proteins in healthy individuals and autoimmune patients. I found that some mutated peptides could trigger immune responses in healthy donors and the immune response induced by some mutated peptides could cross-react with the self peptides. Autoimmune patients were found to have responses to both mutated and self peptides. These data allow the conclusion that DNA somatic mutations may be one of the events that trigger or sustain autoimmune diseases. |
