Biochemical and Biophysical Research Communications, Vol.534, 680-686, 2021
A TCR-like antibody against a proinsulin-containing fusion peptide ameliorates type 1 diabetes in NOD mice
Type 1 diabetes (T1D) is an autoimmune disease caused by destruction of insulin-producing beta cells. The response of autoreactive T cells tor, cell antigens plays a central role in the development of T1D. Recently, fusion peptides composed by insulin C-peptide fragments and other proteins were reported as beta cell target antigens for diabetogenic CD4(+) T cells in non-obese diabetic (NOD) mice. In this study, we generated a T cell-receptor (TCR)-like monoclonal antibody (mAb) against a fusion peptide bound to major histocompatibility complex (MHC) class II component to elucidate the function of the fusion peptides in T1D. In addition, we developed a novel NFAT-GFP TCR reporter system to evaluate the TCR-like mAb. The NFAT-GFP reporter T cells expressing the diabetogenic TCR were specifically activated by the fusion peptide presented on the MHC class II molecules. By using the NFAT-GFP reporter T cells, we showed that the TCR-like mAb blocks the diabetogenic T cell response against the fusion peptide presented on the MHC class II molecules. Furthermore, the development of T1D was ameliorated when prediabetic NOD mice were treated with this mAb. These findings suggest that NFAT-GFP reporter T cells are useful to assess the function of specific TCR and the recognition of fusion peptides by T cells is crucial for the pathogenesis of T1D. (C) 2020 Elsevier Inc. All rights reserved.