Type 1 diabetes (T1D) is an autoimmune disease characterized by immunity against pancreatic islet‐derived proteins. The object of this study was to measure antibody and T‐cell responses against proinsulin (PI), an islet‐derived protein, and to map its dominant T‐cell epitopes.

Antibody responses to proinsulin, insulin, glutamic acid decarboxylase (GAD), protein tyrosine phosphatase IA‐2 and islet‐cell antigen were measured in 116 newly diagnosed diabetic subjects aged 16 to 40 years. T‐cell proliferative responses to proinsulin and proinsulin peptides were measured in 33 of these diabetic subjects and in 21 healthy control subjects.

22% of diabetic subjects but no control subjects expressed antibodies to proinsulin. A strong correlation existed between antibody levels to proinsulin and insulin within diabetic subjects. Similar proportions of diabetic (12%) and healthy (9.5%) subjects displayed T‐cell responses to proinsulin. There was no correlation between antibody and T‐cell responses to proinsulin within subjects. Amino acid region 56 to 72 was identified as the major T‐cell epitope of proinsulin, though significant responses to region 14 to 37 were also present.

Elevated proinsulin autoantibodies in diabetic subjects confirm proinsulin is an important autoantigen in type 1 diabetes. Though elevated cellular immunity to proinsulin protein was not detected, two dominant T‐cell epitopes of proinsulin were identified that span the C‐peptide and insulin junctions. Immunity to proinsulin was lower than that reported for childhood‐onset type 1 diabetes and we propose that, like insulin, proinsulin may be targeted less frequently in adulthood. Copyright © 2002 John Wiley & Sons, Ltd.