T-cell clones from a type-1 diabetes patient respond to insulin secretory granule proteins
Abstract
T LYMPHOCYTES reactive to pancreatic beta-cells are thought to have a central role in the autoimmune process leading to type 1 (insulin-dependent) diabetes, but the molecular targets of these T cells have not yet been defined. As identification of such antigens may enable measures to be developed to prevent the disease, we have characterized an antigen that is recognized by insulinoma membrane-reactive T-cell clones established from a newly diagnosed type-1 diabetes patient. Subcellular fractionation studies using rat insulinoma indicate that the antigenic determinant recognized by one of these clones is an integral membrane component of the insulin secretory granule. After a 5,000-fold purification, we have defined the antigen as a monomer of relative molecular mass 38,000. As granular membrane proteins are transiently exposed on the cell surface during exocytosis, their accessibility to components of the immune system may be a function of the secretory activity of beta-cells.
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Increased frequency of islet-specific autoreactive CD8+ T lymphocytes and decreased regulatory immune function have been associated with type 1 diabetes.
“Increased frequency of islet-specific autoreactive CD8+ T lymphocytes and decreased regulatory immune function have been associated with type 1 diabetes.50”
From Type 1 diabetes (2018) · cites this paper as [50]
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- Authors
- Roep, B. O., Arden, S. D., de vries, R. R. P., & Hutton, J. C.
- Affiliations
- University of Cambridge (GB)
- Venue
- Nature
- Published
- 1990-06
- Volume
- 345
- Issue
- 6276
- Pages
- 632-634
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W1990376539
- Cited by
- 185
- References
- 24
- Citations by year
- 2026: 2 · 2025: 4 · 2024: 2 · 2023: 2 · 2022: 1 · 2021: 5 · 2020: 4 · 2019: 1 · 2018: 3 · 2016: 3 · 2015: 2 · 2014: 2 · 2012: 3
- FWCI
- 9.61
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Diabetes and associated disorders
- Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Keywords
- type 1 diabetes, T cell clones, insulin secretory granules, pancreatic beta cells, autoimmunity, insulinoma, antigen identification, exocytosis, disease prevention
- MeSH terms
- Animals, Antigens, Autoantibodies, Autoantigens, Cell Fractionation, Centrifugation, Density Gradient, Cytoplasmic Granules, Diabetes Mellitus, Type 1, Humans, Insulin, Insulinoma, Intracellular Membranes, Islets of Langerhans, Membrane Proteins, Molecular Weight, Pancreatic Neoplasms, T-Lymphocytes, Tumor Cells, Cultured, Rats
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