Expanded T cells from pancreatic lymph nodes of type 1 diabetic subjects recognize an insulin epitope.

Abstract

In autoimmune type 1 diabetes, pathogenic T lymphocytes are associated with the specific destruction of insulin-producing beta-islet cells. Identification of the autoantigens involved in triggering this process is a central question. Here we examined T cells from pancreatic draining lymph nodes, the site of islet-cell-specific self-antigen presentation. We cloned single T cells in a non-biased manner from pancreatic draining lymph nodes of subjects with type 1 diabetes and from non-diabetic controls. A high degree of T-cell clonal expansion was observed in pancreatic lymph nodes from long-term diabetic patients but not from control subjects. The oligoclonally expanded T cells from diabetic subjects with DR4, a susceptibility allele for type 1 diabetes, recognized the insulin A 1-15 epitope restricted by DR4. These results identify insulin-reactive, clonally expanded T cells from the site of autoinflammatory drainage in long-term type 1 diabetics, indicating that insulin may indeed be the target antigen causing autoimmune diabetes.

• Authors: Sally C Kent, Yahua Chen, Lisa Bregoli, Sue M Clemmings, Norma Sue Kenyon, Camillo Ricordi, Bernhard J Hering, David A Hafler
• Journal: Nature (Nature) Vol. 435 Issue 7039 Pg. 224-8 (May 12 2005) ISSN: 1476-4687 [Electronic] England
• PMID: 15889096 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Epitopes, T-Lymphocyte
• HLA-DR Antigens
• HLA-DRB1 Chains
• Insulin
• Receptors, Antigen, T-Cell

Topics

• Alleles
• Amino Acid Sequence
• Case-Control Studies
• Clone Cells (cytology, immunology)
• Diabetes Mellitus, Type 1 (immunology, pathology)
• Epitopes, T-Lymphocyte (immunology)
• HLA-DR Antigens (immunology)
• HLA-DRB1 Chains
• Humans
• Insulin (immunology)
• Lymph Nodes (cytology, immunology)
• Molecular Sequence Data
• Pancreas (immunology)
• Receptors, Antigen, T-Cell (chemistry, genetics, immunology)
• Substrate Specificity
• T-Lymphocytes (cytology, immunology)