Epitopes described in "Transgenic insulin (B:9-23) T-cell receptor mice develop autoimmune diabetes dependent upon RAG genotype, H-2g7 homozygosity, and insulin 2 gene knockout."

Article Authors:Jean M Jasinski; Liping Yu; Maki Nakayama; Marcella M Li; Myra A Lipes; George S Eisenbarth; Edwin Liu
Article Title:Transgenic insulin (B:9-23) T-cell receptor mice develop autoimmune diabetes dependent upon RAG genotype, H-2g7 homozygosity, and insulin 2 gene knockout.
Reference Detail
Reference ID:1007454
Abstract:A series of recent studies in humans and the NOD mouse model have highlighted the central role that autoimmunity directed against insulin, in particular the insulin B chain 9-23 peptide, may play in the pathogenesis of type 1 diabetes. Both pathogenic and protective T-cell clones recognizing the B:9-23 peptide have been produced. This report describes the successful creation of BDC12-4.1 T-cell receptor (TCR) transgenic mice with spontaneous insulitis in F1 mice (FVB x NOD) and spontaneous diabetes in NOD.RAG(-/-) (backcross 1 generation). Disease progression is heterogeneous and is modified by a series of genetic factors including heterozygosity (H-2(g7)/H-2(q)) versus homozygosity for H-2(g7), the presence of additional T-/B-cell receptor-rearranged genes (RAG(+) versus RAG(-/-)), and the insulin 2 gene knockout (the insulin gene expressed in the NOD thymus). Despite lymphopenia, 40% of H-2(g7/g7) BDC12-4.1 TCR(+) RAG(-/-) Ins2(-/-) mice are diabetic by 10 weeks of age. As few as 13,500 transgenic T-cells from a diabetic TCR(+) RAG(-/-) mouse can transfer diabetes to an NOD.scid mouse. The current study demonstrates that the BDC12-4.1 TCR is sufficient to cause diabetes at NOD backcross 1, bypassing polygenic inhibition of insulitis and diabetogenesis.
Affiliations:Barbara Davis Center for Childhood Diabetes, University of Colorado Health Sciences Center, P.O. Box 6511, MS B140, Aurora, CO 80045-6511, USA.
Reference Type:Literature
PubMed ID:16804066
Journal Volume:55
Article Pages:1978-84
Journal ISSN:0012-1797
Article Chemical List:Insulin;Receptors, Antigen, T-Cell;Interferon-gamma
Article MeSH List:Adoptive Transfer; Animals; CD4-Positive T-Lymphocytes(immunology); CD8-Positive T-Lymphocytes(immunology); Crosses, Genetic; Diabetes Mellitus(genetics; immunology); Diabetes Mellitus, Type 1(genetics); Female; Genes, RAG-1; Heterozygote; Insulin(genetics); Interferon-gamma(blood); Male; Mice; Mice, Inbred NOD; Mice, Knockout; Mice, Transgenic; Receptors, Antigen, T-Cell(deficiency; genetics)
Curation Last Updated:2015-07-30 20:20:44