Proliferative responses to selected peptides of IA-2 in identical twins discordant for Type 1 diabetes

Background The aim of the study was to define T lymphocyte reactivity to se lected peptides of an islet antigen IA-2, associated with Type 1 diabetes. Methods We used 10 peptides selected from the IA-2 molecule due to their pr edicted ability to bind to HLA-DRB1*0401, a Type 1 diabetes-associated alle le. We tested 21 identical twin pairs discordant for the disease and 15 con trol subjects and then followed them prospectively; seven non-diabetic twin s developed diabetes. Results Twins of identical pairs tended to respond to different peptides su ggesting that the T cell response is, to a degree, shaped by non-geneticall y determined factors (p<0.0001). However, there was no difference in the T cell responses between diabetic twins and either their non-diabetic identic al twins or control subjects and the response was heterogenous. T cell resp onses did not differ in those seven non-diabetic twins who developed diabet es from those twins who did not. T cell responses to peptide 11 (amino acid s 502-514) was immunodominant in diabetic twins as well as their nondiabeti c twins and controls; responses were not correlated with HLA, IA-2 antibodi es, age or duration of disease. Conclusion We conclude that T cell responses to selected IA-2 peptides are not genetically determined, heterogeneous, not strictly HLA. controlled and did not distinguish diabetic or prediabetic twins from non-diabetic twins or controls. The identification of an immunodominant T cell response to IA- 2 peptide 502-514 raises the possibility that this, or similar, epitopes ma y be of therapeutic value in disease prevention. Copyright (C) 2000 John Wi ley & Sons, Ltd.