Epitopes described in "Conserved T cell receptor alpha-chain induces insulin autoantibodies."

Article Authors:Masakazu Kobayashi; Jean Jasinski; Edwin Liu; Marcella Li; Dongmei Miao; Li Zhang; Liping Yu; Maki Nakayama; George S Eisenbarth
Article Title:Conserved T cell receptor alpha-chain induces insulin autoantibodies.
Reference Detail
Reference ID:1013546
Abstract:A fundamental question is what are the molecular determinants that lead to spontaneous preferential targeting of specific autoantigens in autoimmune diseases, such as the insulin B:9-23 peptide sequence in type 1 diabetes. Anti-insulin B:9-23 T cell clones isolated from prediabetic NOD islets have a conserved Valpha-segment/Jalpha-segment, but no conservation of the alpha-chain N region and no conservation of the Vbeta-chain. Here, we show that the conserved T cell receptor alpha-chain generates insulin autoantibodies when transgenically or retrogenically introduced into mice without its corresponding Vbeta. We suggest that a major part of the mystery as to why islet autoimmunity develops relates to recognition of a primary insulin peptide by a conserved alpha chain T cell receptor.
Affiliations:Barbara Davis Center for Childhood Diabetes, University of Colorado Health Sciences Center, Aurora, CO 80045, USA.
Reference Type:Literature
PubMed ID:18626021
Journal:Proc Natl Acad Sci U S A
Journal Volume:105
Article Pages:10090-4
Journal ISSN:0027-8424
Article Chemical List:Autoantibodies;DNA Primers;Insulin;Insulin Antibodies;Receptors, Antigen, T-Cell, alpha-beta;Interferon-gamma
Article MeSH List:Adoptive Transfer; Animals; Autoantibodies(biosynthesis); Base Sequence; Clone Cells(immunology); Conserved Sequence; DNA Primers(genetics); Female; Genes, T-Cell Receptor alpha; Genes, T-Cell Receptor beta; Insulin(immunology); Insulin Antibodies(biosynthesis); Interferon-gamma(biosynthesis); Islets of Langerhans(immunology; pathology); Male; Mice; Mice, Inbred NOD; Mice, Knockout; Mice, SCID; Mice, Transgenic; Receptors, Antigen, T-Cell, alpha-beta(genetics; metabolism); T-Lymphocytes(immunology)
Curation Last Updated:2015-07-30 20:28:23