title: Molecular targeting of islet autoantigens.
abstract: Type 1 diabetes of man and animal models results from immune-mediated specific beta cell destruction. Multiple islet antigens are targets of autoimmunity and most of these are not beta cell specific. Immune responses to insulin appear to be essential for the development of diabetes of the NOD mouse. In this review, we will emphasize the unusual manner in which selected autoantigenic peptides (particularly the recently discovered target of BDC2.5 T cells [chromagranin A]) are presented and recognized by autoreactive CD4(+) T cell receptors. We hypothesize that "unusual" structural interactions of specific trimolecular complexes (MHC class II, peptide, and T cell receptors) are fundamental to the escape from the thymus of autoreactive T cells able to cause type 1 diabetes.
authors.affiliation: National Jewish Health, Denver, CO 80206, USA.
authors.forename: Brian
authors.initials: B
authors.lastname: Stadinski
authors.forename: John
authors.initials: J
authors.lastname: Kappler
authors.forename: George S
authors.initials: GS
authors.lastname: Eisenbarth
mesh_terms: D000818:Animals; D001324:Autoantigens / Q000276:immunology*; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology*; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D006801:Humans; D007515:Islets of Langerhans / Q000276:immunology*; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D001324:Autoantigens; D000949:Histocompatibility Antigens Class II; D011948:Receptors, Antigen, T-Cell