Unique features in the presentation of insulin epitopes in autoimmune diabetes: an update

- Insulin is required to initiate autoimmune diabetes in NOD mice.
- NOD mice and human patients share common features of insulin autoreactivity.
- Antigen presentation of insulin occurs in various lymphoid organs.
- Insulin presentation profoundly influences T and B lymphocyte activity.
- Insulin is a therapeutic target for treating autoimmune diabetes.

Although an autoimmune disease involves diverse self-antigens, the initiation stage may require recognition of a limited number. This concept is verified in the non-obese diabetic (NOD) mouse model of autoimmune diabetes, in which strong evidence points to insulin as the prime antigen. The NOD mouse bears the I-Ag7 class II-MHC molecules (MHCII) that share common biochemical features and peptidome selection with the human diabetes-susceptible HLA-DQ8. Furthermore, both NOD mice and patients with type 1 diabetes (T1D) display an early appearance of insulin autoantibodies (IAAs) and subsequent insulin-reactive T cell infiltration into the islets. Therefore, a better understanding of insulin presentation is crucial for assessing disease pathogenesis and therapeutic intervention. Here, we summarize recent advances in insulin presentation events that underlie the essential role of this autoantigen in driving autoimmune diabetes.