1. Susceptible MHC alleles, not background genes, select an autoimmune T cell reactivity.
- Author
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Stratmann, Thomas, Martin-Orozco, Natalia, Mallet-Designe, Valerie, Poirot, Laurent, McGavern, Dorian, Losyev, Grigoriy, Dobbs, Cathleen M., Oldstone, Michael B.A., Yoshida, Kenji, Kikutani, Hitoshi, Mathis, Diane, Benoist, Christophe, Haskins, Kathryn, and Teyton, Luc
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MAJOR histocompatibility complex , *T cells , *AUTOIMMUNITY , *PANCREAS , *DIABETES - 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 oft 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-2[supg7] 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. [ABSTRACT FROM AUTHOR]
- Published
- 2003
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