Research Of HLA-A2 Restricted T Cell Epitopes About Autoantigen Of Type 1 Diabetes

【Abstract】Type 1 diabetes arises from the selective destruction of pancreatic isletβ-cells through a coordinated effort by T-cells of the immune system. Identi?cation of these molecular targets provides insight into the pathogenic process, diagnostic assays, and potential therapeutic agents. In humans, fewβ-cell epitopes have been reported, thereby limiting the study ofβ-cell–speci?c CTLs (cytotoxic T lymphocytes) in type 1 diabetes. To identify additional epitopes, HLA class I peptide af?nity algorithms were used to identify a panel of peptides derived from theβ-cell proteins (IAPP, GFAP, IGRP, insulin, IA-2,GAD65 and ZnT8 ). 36 HLA-A*0201 candidate peptide epitopes were analyzed using SYFPEITHI and BIMAS algorithms to identify for screening. We use peptide binding assays, found that the predicted binding af?nity ofβ-cell peptides to HLA-A*0201 did not correlate well with the actual binding af?nity.Through dissociation rate ofβ-cell peptides from HLA-A*0201, we found peptides tested—InsulinB10, IGRP228-236, GFAP143-151, IA-2 172-180 and ZnT8 107-115 produced HLA complexes that were stable over a 4h period (~10% dissociation in 4h). Those high af?nity binding and low dissociation rate peptides maybe have good potential immunogenicity. These epitopes may be important in the pathogenesis of type 1 diabetes.