Expanded T cells from pancreatic lymph nodes of type 1 diabetic subjects recognize an insulin epitope.
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.
Kent
Sally C
SC
Center for Neurologic Diseases, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA.
Chen
Yahua
Y
Bregoli
Lisa
L
Clemmings
Sue M
SM
Kenyon
Norma Sue
NS
Ricordi
Camillo
C
Hering
Bernhard J
BJ
Hafler
David A
DA
D000483:Alleles; D000595:Amino Acid Sequence; D016022:Case-Control Studies; D002999:Clone Cells / Q000166:cytology / Q000276:immunology; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology* / Q000473:pathology; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D006684:HLA-DR Antigens / Q000276:immunology; D059811:HLA-DRB1 Chains; D006801:Humans; D007328:Insulin / Q000276:immunology*; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology*; D008969:Molecular Sequence Data; D010179:Pancreas / Q000276:immunology*; D011948:Receptors, Antigen, T-Cell / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D013379:Substrate Specificity; D013601:T-Lymphocytes / Q000166:cytology* / Q000276:immunology*
D018984:Epitopes, T-Lymphocyte; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; D007328:Insulin; D011948:Receptors, Antigen, T-Cell