Epitopes described in "Pathogenic CD4⁺ T cells recognizing an unstable peptide of insulin are directly recruited into islets bypassing local lymph nodes."

Article Authors:James F Mohan; Boris Calderon; Mark S Anderson; Emil R Unanue
Article Title:Pathogenic CD4⁺ T cells recognizing an unstable peptide of insulin are directly recruited into islets bypassing local lymph nodes.
Reference Detail
Reference ID:1026912
Abstract:In the nonobese diabetic mouse, a predominant component of the autoreactive CD4(+) T cell repertoire is directed against the B:9-23 segment of the insulin B chain. Previous studies established that the majority of insulin-reactive T cells specifically recognize a weak peptide-MHC binding register within the B:9-23 segment, that to the 12-20 register. These T cells are uniquely stimulated when the B:9-23 peptide, but not the insulin protein, is offered to antigen presenting cells (APCs). Here, we report on a T cell receptor (TCR) transgenic mouse (8F10) that offers important new insights into the biology of these unconventional T cells. Many of the 8F10 CD4(+) T cells escaped negative selection and were highly pathogenic. The T cells were directly recruited into islets of Langerhans, where they established contact with resident intra-islet APCs. Immunogenic insulin had to be presented in order for the T cells to localize and cause disease. These T cells bypassed an initial priming stage in the pancreatic lymph node thought to precede islet T cell entry. 8F10 T cells induced the production of antiinsulin antibodies and islets contained immunoglobulin (IgG) deposited on cells and along the vessel walls.
Affiliations:Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110.
Reference Type:Literature
PubMed ID:24127484
Journal:J Exp Med
Journal Volume:210
Article Pages:2403-14
Journal ISSN:0022-1007
Article Chemical List:Insulin;Peptides;Receptors, Antigen, T-Cell
Article MeSH List:Amino Acid Sequence; Animals; CD4-Positive T-Lymphocytes(pathology); Female; Insulin(chemistry; immunology); Islets of Langerhans(immunology; pathology); Lymph Nodes(immunology; pathology); Mice; Mice, Inbred NOD; Mice, Transgenic; Molecular Sequence Data; Peptides(chemistry; immunology); Protein Stability; Receptors, Antigen, T-Cell(metabolism)
Curation Last Updated:2015-07-30 20:48:48