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A peptide of glutamic acid decarboxylase 65 can recruit and expand a diabetogenic T cell clone, BDC2.5, in the pancreas

Academic Article
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Overview

authors

  • Dai, Yang D.
  • Jensen, K. P.
  • Lehuen, A.
  • Masteller, E. L.
  • Bluestone, J. A.
  • Wilson, D. B.
  • Sercarz, E. E.

publication date

  • September 2005

journal

  • Journal of Immunology  Journal

abstract

  • Self peptide-MHC ligands create and maintain the mature T cell repertoire by positive selection in the thymus and by homeostatic proliferation in the periphery. A low affinity/avidity interaction among T cells, self peptides, and MHC molecules has been suggested for these events, but it remains unknown whether or how this self-interaction is involved in tolerance and/or autoimmunity. Several lines of evidence implicate the glutamic acid decarboxylase 65 (GAD-65) peptide, p524-543, as a specific, possibly low affinity, stimulus for the spontaneously arising, diabetogenic T cell clone BDC2.5. Interestingly, BDC2.5 T cells, which normally are unresponsive to p524-543 stimulation, react to the peptide when provided with splenic APC obtained from mice immunized with the same peptide, p524-543, but not, for example, with hen egg white lysozyme. Immunization with p524-543 increases the susceptibility of the NOD mice to type 1 diabetes induced by the adoptive transfer of BDC2.5 T cells. In addition, very few CFSE-labeled BDC2.5 T cells divide in the recipient's pancreas after transfer into a transgenic mouse that overexpresses GAD-65 in B cells, whereas they divide vigorously in the pancreas of normal NOD recipients. A special relationship between the BDC2.5 clone and the GAD-65 molecule is further demonstrated by generation of a double-transgenic mouse line carrying both the BDC2.5 TCR and GAD-65 transgenes, in which a significant reduction of BDC2.5 cells in the pancreas has been observed, presumably due to tolerance induction. These data suggest that unique and/or altered processing of self Ags may play an essential role in the development and expansion of autoreactive T cells.

subject areas

  • Adoptive Transfer
  • Animals
  • Autoimmunity
  • Cell Proliferation
  • Chemotaxis, Leukocyte
  • Clone Cells
  • Diabetes Mellitus, Type 1
  • Glutamate Decarboxylase
  • Immune Tolerance
  • Mice
  • Mice, Inbred NOD
  • Mice, Transgenic
  • Pancreas
  • Peptide Fragments
  • T-Lymphocytes
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Identity

International Standard Serial Number (ISSN)

  • 0022-1767

Digital Object Identifier (DOI)

  • 10.4049/jimmunol.175.6.3621

PubMed ID

  • 16148106
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Additional Document Info

start page

  • 3621

end page

  • 3627

volume

  • 175

issue

  • 6

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