1. Susceptible MHC alleles, not background genes, select an autoimmune T cell reactivity.
- Author
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Stratmann T, Martin-Orozco N, Mallet-Designe V, Poirot L, McGavern D, Losyev G, Dobbs CM, Oldstone MB, Yoshida K, Kikutani H, Mathis D, Benoist C, Haskins K, and Teyton L
- Subjects
- Animals, Autoantigens immunology, CD4-Positive T-Lymphocytes physiology, Diabetes Mellitus, Type 1 metabolism, Female, Haplotypes, Hybridomas cytology, Hybridomas immunology, Hybridomas metabolism, Mice, Mice, Inbred NOD, Mice, Transgenic, Receptors, Antigen, T-Cell genetics, Receptors, Antigen, T-Cell metabolism, Thymus Gland cytology, Thymus Gland metabolism, Alleles, Autoimmunity, CD4-Positive T-Lymphocytes immunology, Diabetes Mellitus, Type 1 immunology, Major Histocompatibility Complex genetics
- 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.
- Published
- 2003
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