論文 - 詳細
| RRC ID | 63187 |
|---|---|
| 著者 | Matsumoto Y, Kishida K, Matsumoto M, Matsuoka S, Kohyama M, Suenaga T, Arase H. |
| タイトル | A TCR-like antibody against a proinsulin-containing fusion peptide ameliorates type 1 diabetes in NOD mice. |
| ジャーナル | 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. |
| 巻・号 | 534 |
| ページ | 680-686 |
| 公開日 | 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 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 4 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | 293T(RCB2202) |