التفاصيل البيبلوغرافية
| العنوان: |
Islet-Derived CD4 T Cells Targeting Proinsulin in Human Autoimmune Diabetes |
| المؤلفون: |
Michels, Aaron W, Landry, Laurie G, McDaniel, Kristen A, Yu, Liping, Campbell-Thompson, Martha, Kwok, William W, Jones, Kenneth L, Gottlieb, Peter A, Kappler, John W, Tang, Qizhi, Roep, Bart O, Atkinson, Mark A, Mathews, Clayton E, Nakayama, Maki |
| المصدر: |
Diabetes, vol 66, iss 3 |
| بيانات النشر: |
eScholarship, University of California |
| سنة النشر: |
2017 |
| المجموعة: |
University of California: eScholarship |
| مصطلحات موضوعية: |
Diabetes, Autoimmune Disease, 2.1 Biological and endogenous factors, Aetiology, Metabolic and endocrine, Adolescent, Autoantigens, C-Peptide, CD4-Positive T-Lymphocytes, Child, Diabetes Mellitus, Type 1, Female, HLA-DQ Antigens, HLA-DR Antigens, Humans, Insulin, Insulin-Secreting Cells, Islets of Langerhans, Peptide Fragments, Proinsulin, Protein Precursors, Receptors, Antigen, T-Cell, Young Adult, Medical and Health Sciences, Endocrinology & Metabolism |
| جغرافية الموضوع: |
722 - 734 |
| الوصف: |
Type 1 diabetes results from chronic autoimmune destruction of insulin-producing β-cells within pancreatic islets. Although insulin is a critical self-antigen in animal models of autoimmune diabetes, due to extremely limited access to pancreas samples, little is known about human antigenic targets for islet-infiltrating T cells. Here we show that proinsulin peptides are targeted by islet-infiltrating T cells from patients with type 1 diabetes. We identified hundreds of T cells from inflamed pancreatic islets of three young organ donors with type 1 diabetes with a short disease duration with high-risk HLA genes using a direct T-cell receptor (TCR) sequencing approach without long-term cell culture. Among 85 selected CD4 TCRs tested for reactivity to preproinsulin peptides presented by diabetes-susceptible HLA-DQ and HLA-DR molecules, one T cell recognized C-peptide amino acids 19-35, and two clones from separate donors responded to insulin B-chain amino acids 9-23 (B:9-23), which are known to be a critical self-antigen-driving disease progress in animal models of autoimmune diabetes. These B:9-23-specific T cells from islets responded to whole proinsulin and islets, whereas previously identified B:9-23 responsive clones from peripheral blood did not, highlighting the importance of proinsulin-specific T cells in the islet microenvironment. |
| نوع الوثيقة: |
article in journal/newspaper |
| وصف الملف: |
application/pdf |
| اللغة: |
unknown |
| العلاقة: |
qt3hj3w3zr; https://escholarship.org/uc/item/3hj3w3zrTest |
| الإتاحة: |
https://escholarship.org/uc/item/3hj3w3zrTest |
| حقوق: |
public |
| رقم الانضمام: |
edsbas.651D9C15 |
| قاعدة البيانات: |
BASE |
