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Susceptible MHC alleles, not background genes, select an autoimmune T cell reactivity

Academic Article
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Overview

authors

  • Stratmann, T.
  • Martin-Orozco, N.
  • Mallet-Designe, V.
  • Poirot, L.
  • McGavern, D.
  • Losyev, G.
  • Dobbs, C. M.
  • Oldstone, Michael
  • Yoshida, K.
  • Kikutani, H.
  • Mathis, D.
  • Benoist, C.
  • Haskins, K.
  • Teyton, Luc

publication date

  • September 2003

journal

  • Journal of Clinical Investigation  Journal

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.

subject areas

  • Alleles
  • Animals
  • Autoantigens
  • Autoimmunity
  • CD4-Positive T-Lymphocytes
  • Diabetes Mellitus, Type 1
  • Female
  • Haplotypes
  • Hybridomas
  • Major Histocompatibility Complex
  • Mice
  • Mice, Inbred NOD
  • Mice, Transgenic
  • Receptors, Antigen, T-Cell
  • Thymus Gland
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Identity

PubMed Central ID

  • PMC193666

International Standard Serial Number (ISSN)

  • 0021-9738

Digital Object Identifier (DOI)

  • 10.1172/jci200318337

PubMed ID

  • 12975475
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Additional Document Info

start page

  • 902

end page

  • 914

volume

  • 112

issue

  • 6

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