| RRC ID |
63187
|
| Author |
Matsumoto Y, Kishida K, Matsumoto M, Matsuoka S, Kohyama M, Suenaga T, Arase H.
|
| Title |
A TCR-like antibody against a proinsulin-containing fusion peptide ameliorates type 1 diabetes in NOD mice.
|
| Journal |
Biochem Biophys Res Commun
|
| Abstract |
Type 1 diabetes (T1D) is an autoimmune disease caused by destruction of insulin-producing β cells. The response of autoreactive T cells to β 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 β 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 pre-diabetic 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.
|
| Volume |
534
|
| Pages |
680-686
|
| Published |
2021-1-1
|
| DOI |
10.1016/j.bbrc.2020.11.019
|
| PII |
S0006-291X(20)32063-5
|
| PMID |
33208230
|
| MeSH |
Animals
Antibodies, Monoclonal / pharmacology*
C-Peptide / antagonists & inhibitors
C-Peptide / genetics
C-Peptide / immunology
Diabetes Mellitus, Experimental / etiology
Diabetes Mellitus, Experimental / immunology
Diabetes Mellitus, Experimental / prevention & control
Diabetes Mellitus, Type 1 / etiology
Diabetes Mellitus, Type 1 / immunology
Diabetes Mellitus, Type 1 / prevention & control*
Disease Progression
Histocompatibility Antigens Class II / genetics
Histocompatibility Antigens Class II / immunology
Mice
Mice, Inbred NOD
Proinsulin / antagonists & inhibitors*
Proinsulin / genetics
Proinsulin / immunology*
Receptors, Antigen, T-Cell / immunology*
Recombinant Fusion Proteins / genetics
Recombinant Fusion Proteins / immunology
T-Lymphocytes / immunology
|
| IF |
2.985
|
| Resource |
| Human and Animal Cells |
293T(RCB2202) |
