Restricted islet-cell reactive T cell repertoire of early pancreatic islet infiltrates in NOD mice.
The mechanisms responsible for initiating autoimmune diabetes remain obscure. Here, we describe a method for identifying both the alpha- and beta-chains of the T cell receptor (TCR) from individual pancreatic islet-infiltrating T cells at the earliest stages of disease in nonobese diabetic mice (NOD). Analysis of the TCR repertoire of these early islet infiltrates reveals enrichment for a small subset of TCR sequences. Reconstitution of these TCR in vitro demonstrates that these receptors confer reactivity to islet cells but not to the well characterized autoantigens, glutamic acid decarboxylase (GAD65) and insulin. Thus, autoimmune diabetes in NOD may be initiated by a limited number of antigens distinct from GAD65 and insulin.
Baker
Felix J
FJ
Howard Hughes Medical Institute and Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305, USA.
Lee
Mark
M
Chien
Yueh-hsiu
YH
Davis
Mark M
MM
D000595:Amino Acid Sequence; D000818:Animals; D001324:Autoantigens; D022801:Complementarity Determining Regions / Q000235:genetics; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics / Q000276:immunology*; D019673:Genes, T-Cell Receptor alpha; D019674:Genes, T-Cell Receptor beta; D005968:Glutamate Decarboxylase / Q000276:immunology; D066298:In Vitro Techniques; D007328:Insulin / Q000276:immunology; D007515:Islets of Langerhans / Q000276:immunology*; D007527:Isoenzymes / Q000276:immunology; D051379:Mice; D016688:Mice, Inbred NOD; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction / Q000379:methods; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D013601:T-Lymphocytes / Q000276:immunology*
D001324:Autoantigens; D022801:Complementarity Determining Regions; D007328:Insulin; D007527:Isoenzymes; D016693:Receptors, Antigen, T-Cell, alpha-beta; D005968:Glutamate Decarboxylase; C401141:glutamate decarboxylase 2