Epitopes described in "Germline TRAV5D-4 T-cell receptor sequence targets a primary insulin peptide of NOD mice."

Article Authors:Maki Nakayama; Todd Castoe; Tomasz Sosinowski; XiangLing He; Kelly Johnson; Kathryn Haskins; Dario A A Vignali; Laurent Gapin; David Pollock; George S Eisenbarth
Article Title:Germline TRAV5D-4 T-cell receptor sequence targets a primary insulin peptide of NOD mice.
Reference Detail
Reference ID:1022942
Abstract:There is accumulating evidence that autoimmunity to insulin B chain peptide, amino acids 9-23 (insulin B:9-23), is central to development of autoimmune diabetes of the NOD mouse model. We hypothesized that enhanced susceptibility to autoimmune diabetes is the result of targeting of insulin by a T-cell receptor (TCR) sequence commonly encoded in the germline. In this study, we aimed to demonstrate that a particular V gene TRAV5D-4 with multiple junction sequences is sufficient to induce anti-islet autoimmunity by studying retrogenic mouse lines expressing -chains with different V TRAV genes. Retrogenic NOD strains expressing V TRAV5D-4 -chains with many different complementarity determining region (CDR) 3 sequences, even those derived from TCRs recognizing islet-irrelevant molecules, developed anti-insulin autoimmunity. Induction of insulin autoantibodies by TRAV5D-4 -chains was abrogated by the mutation of insulin peptide B:9-23 or that of two amino acid residues in CDR1 and 2 of the TRAV5D-4. TRAV13-1, the human ortholog of murine TRAV5D-4, was also capable of inducing in vivo anti-insulin autoimmunity when combined with different murine CDR3 sequences. Targeting primary autoantigenic peptides by simple germline-encoded TCR motifs may underlie enhanced susceptibility to the development of autoimmune diabetes.
Affiliations:Barbara Davis Center for Childhood Diabetes, University of ColoradoSchool of Medicine, Aurora, CO, USA. maki.nakayama@ucdenver.edu.
Reference Type:Literature
PubMed ID:22315318
Journal Volume:61
Article Pages:857-65
Journal ISSN:1939-327X
Article Chemical List:gov.nih.nlm.ncbi.www.jaxb.impl.NameOfSubstanceImpl@1dc50679;gov.nih.nlm.ncbi.www.jaxb.impl.NameOfSubstanceImpl@722c0133;gov.nih.nlm.ncbi.www.jaxb.impl.NameOfSubstanceImpl@2702f5d4;gov.nih.nlm.ncbi.www.jaxb.impl.NameOfSubstanceImpl@3359454e;gov.nih.nlm.ncbi.www.jaxb.impl.NameOfSubstanceImpl@29d51e38
Article MeSH List:Animals; Autoimmunity; Complementarity Determining Regions(genetics; metabolism); Diabetes Mellitus, Type 1(genetics); Gene Expression Regulation(physiology); Germ-Line Mutation; Insulin(genetics; immunology; metabolism); Mice; Mice, Inbred NOD; Mice, Knockout; Peptide Fragments(genetics; immunology; metabolism); Receptors, Antigen, T-Cell, alpha-beta(genetics; metabolism); T-Cell Antigen Receptor Specificity(genetics); Time Factors
Curation Last Updated:2015-01-18 20:13:16