title: MHC-linked protection from diabetes dissociated from clonal deletion of T cells.
abstract: The I-E molecule of the major histocompatibility complex (MHC) can prevent the spontaneous development of diabetes in nonobese diabetic (NOD) mice. The mechanism of this protection has been investigated by breeding wild-type and promoter-mutated E kappa alpha transgenes onto the NOD genetic background. Animals carrying the various mutated transgenes expressed I-E on different subsets of immunocompetent cells, and thus cells important for the I-E protective effect could be identified. Although the wild-type transgene prevented the infiltration of lymphocytes into pancreatic islets, none of the mutants did. However, all of the transgenes could mediate the intrathymic elimination of T cells bearing antigen receptors with variable regions that recognize I-E. Thus, the I-E molecule does not protect NOD mice from diabetes simply by inducing the deletion of self-reactive T cells.
authors.affiliation: Laboratoire de Genetique Moléculaire des Eucaryotes du CNRS, Faculté de Médecine, Strasbourg, France.
authors.forename: J
authors.initials: J
authors.lastname: Böhme
authors.forename: B
authors.initials: B
authors.lastname: Schuhbaur
authors.forename: O
authors.initials: O
authors.lastname: Kanagawa
authors.forename: C
authors.initials: C
authors.lastname: Benoist
authors.forename: D
authors.initials: D
authors.lastname: Mathis
mesh_terms: D000818:Animals; D002999:Clone Cells; D003433:Crosses, Genetic; D003921:Diabetes Mellitus, Experimental / Q000276:immunology* / Q000517:prevention & control; D005802:Genes, MHC Class II; D000949:Histocompatibility Antigens Class II / Q000235:genetics / Q000276:immunology*; D007515:Islets of Langerhans / Q000276:immunology; D008285:Major Histocompatibility Complex; D051379:Mice; D008817:Mice, Mutant Strains; D008822:Mice, Transgenic; D009154:Mutation; D011401:Promoter Regions, Genetic; D011948:Receptors, Antigen, T-Cell / Q000235:genetics; D013601:T-Lymphocytes / Q000276:immunology*; D013950:Thymus Gland / Q000276:immunology
chemical_list: D000949:Histocompatibility Antigens Class II; C024138:I-E-antigen; D011948:Receptors, Antigen, T-Cell