Islet amyloid polypeptide is not a target antigen for CD8+ T-cells in type 2 diabetes

ABSTRACT

Type 2 diabetes [T2D] is a chronic metabolic disorder in which beta-cells are destroyed. The islet amyloid polypeptide [IAPP] produced by beta-cells has been reported to influence beta-cell destruction. To evaluate if IAPP can act as an autoantigen and therefore, to see if CD8+ T-cells specific for this protein might be present in T2D patients. Peripheral blood mononuclear cells [PBMC] were obtained from human leukocyte antigen [HLA]-A2+ T2D patients and non-diabetic healthy subjects. Cells were then screened for peptide recognition using ELISPOT assay for the presence of IFN-gamma producing CD8+ T-cells against two HLA Class I-restricted epitopes derived from IAPP [IAPP5-13 and IAPP9-17] and common viral antigenic minimal epitopes Flu MP 58-66, CMV495-503, EBV280-288 and HIV77-85 as controls. A total of 36.4% of patients and 56.2% of healthy subjects showed a response against IAPP5-13 peptide. No significant difference in response against this peptide was noted between the patients and the healthy donors. With respect to peptide IAPP9-17, although healthy subjects showed a higher mean number of spot forming cells than the patients, the difference was not significant; 36.4% of patients and 37.5% of controls responded to this peptide. The response of healthy subjects to the common viral peptides was stronger than that of the patients, though the result was not significant. It is unlikely that IAPP would be a target for CD8+ T-cells in diabetic patients; however, the trend observed toward a lower response of T2D patients against IAPP and common viral peptides may imply a decreased immune response in these patients