Islet-Derived CD4 T Cells Targeting Proinsulin in Human Autoimmune Diabetes.
Diabetes
; 66(3): 722-734, 2017 03.
Article
en En
| MEDLINE
| ID: mdl-27920090
ABSTRACT
Type 1 diabetes results from chronic autoimmune destruction of insulin-producing ß-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 (B9-23), which are known to be a critical self-antigen-driving disease progress in animal models of autoimmune diabetes. These B9-23-specific T cells from islets responded to whole proinsulin and islets, whereas previously identified B9-23 responsive clones from peripheral blood did not, highlighting the importance of proinsulin-specific T cells in the islet microenvironment.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Fragmentos de Péptidos
/
Proinsulina
/
Precursores de Proteínas
/
Autoantígenos
/
Receptores de Antígenos de Linfocitos T
/
Linfocitos T CD4-Positivos
/
Islotes Pancreáticos
/
Diabetes Mellitus Tipo 1
/
Insulina
Límite:
Adolescent
/
Adult
/
Child
/
Female
/
Humans
Idioma:
En
Revista:
Diabetes
Año:
2017
Tipo del documento:
Article
País de afiliación:
Colombia