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Glucagon-reactive islet-infiltrating CD8 T cells in NOD mice.
- Source :
-
Immunology [Immunology] 2015 Apr; Vol. 144 (4), pp. 631-40. - Publication Year :
- 2015
-
Abstract
- Type 1 diabetes is characterized by T-cell-mediated destruction of the insulin-producing β cells in pancreatic islets. A number of islet antigens recognized by CD8 T cells that contribute to disease pathogenesis in non-obese diabetic (NOD) mice have been identified; however, the antigenic specificities of the majority of the islet-infiltrating cells have yet to be determined. The primary goal of the current study was to identify candidate antigens based on the level and specificity of expression of their genes in mouse islets and in the mouse β cell line MIN6. Peptides derived from the candidates were selected based on their predicted ability to bind H-2K(d) and were examined for recognition by islet-infiltrating T cells from NOD mice. Several proteins, including those encoded by Abcc8, Atp2a2, Pcsk2, Peg3 and Scg2, were validated as antigens in this way. Interestingly, islet-infiltrating T cells were also found to recognize peptides derived from proglucagon, whose expression in pancreatic islets is associated with α cells, which are not usually implicated in type 1 diabetes pathogenesis. However, type 1 diabetes patients have been reported to have serum autoantibodies to glucagon, and NOD mouse studies have shown a decrease in α cell mass during disease pathogenesis. Our finding of islet-infiltrating glucagon-specific T cells is consistent with these reports and suggests the possibility of α cell involvement in development and progression of disease.<br /> (© 2014 John Wiley & Sons Ltd.)
- Subjects :
- Animals
Autoantigens metabolism
Autoimmunity
CD8-Positive T-Lymphocytes metabolism
Cell Line, Tumor
Computational Biology
Diabetes Mellitus, Type 1 metabolism
Disease Models, Animal
Enzyme-Linked Immunospot Assay
Epitope Mapping
Epitopes, T-Lymphocyte immunology
Epitopes, T-Lymphocyte metabolism
H-2 Antigens immunology
H-2 Antigens metabolism
Interferon-gamma metabolism
Interferon-gamma Release Tests
Islets of Langerhans metabolism
Mice, Inbred NOD
Proglucagon metabolism
Protein Binding
Autoantigens immunology
CD8-Positive T-Lymphocytes immunology
Diabetes Mellitus, Type 1 immunology
Islets of Langerhans immunology
Proglucagon immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1365-2567
- Volume :
- 144
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Immunology
- Publication Type :
- Academic Journal
- Accession number :
- 25333865
- Full Text :
- https://doi.org/10.1111/imm.12415