Type 1A diabetes is an autoimmune disease that specifically affects beta cells within the pancreas and researchers have long asked why only certain organs are targeted in autoimmune disease.
In so-called NOD mice (an animal model of type 1 diabetes) T and B cells that infiltrate the pancreatic islets have been shown to target insulin B chain amino acids 9?23 (insulin B:9?23), and NOD mice lacking insulin B:9?23 are protected from diabetes.
This suggests that insulin, specifically the insulin B:9?23 sequence, may be essential for the initiation of spontaneous diabetes in NOD mice.
In the July 2 issue of the Journal of Clinical Investigation, George Eisenbarth and colleagues posed the question: In which tissue would expression of the native insulin sequence restore anti-insulin autoimmunity” The authors found that transplanted islet cells, but not bone marrow cells, expressing native B16:Y insulin (tyrosine at position 16 of insulin B chain) restored anti-insulin autoimmunity in mice that lacked native insulin genes. In addition, immunization with the native B16:Y insulin B:9?23 peptide, but not a mutated B16:A insulin B:9?23 peptide (alanine at position 16 of insulin B chain), rendered CD4+ T cells able to rapidly transfer diabetes to these animals when the recipient mouse also had the native B16:Y insulin B:9?23 sequence in its islets. The data demonstrate the dependence on just a single amino acid change (alanine versus tyrosine) in insulin B:9?23 for the development of anti-islet cell autoimmunity in a mouse model of type 1 diabetes.
TITLE: Priming and effector dependence on insulin B:9?23 peptide in NOD islet autoimmunity