title: Susceptible MHC alleles, not background genes, select an autoimmune T cell reactivity.
abstract: To detect and characterize autoreactive T cells in diabetes-prone NOD mice, we have developed a multimeric MHC reagent with high affinity for the BDC-2.5 T cell receptor, which is reactive against a pancreatic autoantigen. A distinct population of T cells is detected in NOD mice that recognizes the same MHC/peptide target. These T cells are positively selected in the thymus at a surprisingly high frequency and exported to the periphery. They are activated specifically in the pancreatic LNs, demonstrating an autoimmune specificity that recapitulates that of the BDC-2.5 cell. These phenomena are also observed in mouse lines that share with NOD the H-2g7 MHC haplotype but carry diabetes-resistance background genes. Thus, a susceptible haplotype at the MHC seems to be the only element required for the selection and emergence of autoreactive T cells, without requiring other diabetogenic loci from the NOD genome.
authors.affiliation: Department of Immunology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA.
authors.forename: Thomas
authors.initials: T
authors.lastname: Stratmann
authors.forename: Natalia
authors.initials: N
authors.lastname: Martin-Orozco
authors.forename: Valérie
authors.initials: V
authors.lastname: Mallet-Designe
authors.forename: Laurent
authors.initials: L
authors.lastname: Poirot
authors.forename: Dorian
authors.initials: D
authors.lastname: McGavern
authors.forename: Grigoriy
authors.initials: G
authors.lastname: Losyev
authors.forename: Cathleen M
authors.initials: CM
authors.lastname: Dobbs
authors.forename: Michael B A
authors.initials: MB
authors.lastname: Oldstone
authors.forename: Kenji
authors.initials: K
authors.lastname: Yoshida
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Kikutani
authors.forename: Diane
authors.initials: D
authors.lastname: Mathis
authors.forename: Christophe
authors.initials: C
authors.lastname: Benoist
authors.forename: Kathryn
authors.initials: K
authors.lastname: Haskins
authors.forename: Luc
authors.initials: L
authors.lastname: Teyton
mesh_terms: D000483:Alleles; D000818:Animals; D001324:Autoantigens / Q000276:immunology; D015551:Autoimmunity; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000502:physiology; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology* / Q000378:metabolism; D005260:Female; D006239:Haplotypes; D006825:Hybridomas / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D008285:Major Histocompatibility Complex / Q000235:genetics*; D051379:Mice; D016688:Mice, Inbred NOD; D008822:Mice, Transgenic; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000378:metabolism; D013950:Thymus Gland / Q000166:cytology / Q000378:metabolism
chemical_list: D001324:Autoantigens; D011948:Receptors, Antigen, T-Cell