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N-terminal flanking residues of a diabetes-associated GAD65 determinant are necessary for activation of antigen-specific T cells in diabetes-resistant mice

Academic Article
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Overview

authors

  • Dai, Yang D.
  • Jensen, K. P.
  • Marrero, I.
  • Li, N.
  • Quinn, A.
  • Sercarz, E. E.

publication date

  • April 2008

journal

  • European Journal of Immunology  Journal

abstract

  • A diabetes-associated peptide in the glutamic acid decarboxylase 65 (GAD65) molecule, p524-543, activates two distinct populations of T cells, which apparently play opposite roles in the development of diabetes in NOD mice. By comparing the fine specificity of these two T cell repertoires using a nested set of truncated peptides that cover the p524-543 region, we found, surprisingly, that all clones recognized the same core within this peptide, p530-539. The core itself was non-immunogenic, but the residues flanking this shared sequence played the crucial role in selecting T cells to activate. A peptide missing N-terminal flanking residues at position 528 and 529 was stimulatory in NOD but not in MHC-matched, NOD-resistant (NOR) mice, suggesting that a protective response in the resistant mice may require T cell recognition of one or more of the N-terminal flanking residues. T cell repertoire studies demonstrated selective clonal expansions within the BV4 TCR family that dominates the p524-543 response in NOD but not in NOR mice. These data suggest that processing or trimming events affecting T cell recognition of very few flanking residues of diabetes-associated determinants might be involved in the protective response in NOR mice.

subject areas

  • Animals
  • Antigens
  • DNA, Intergenic
  • Diabetes Mellitus
  • Glutamate Decarboxylase
  • Immunization
  • Lymphocyte Activation
  • Mice
  • Peptide Fragments
  • Receptors, Antigen, T-Cell
  • T-Lymphocytes
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Research

keywords

  • GAD65
  • T cell repertoire
  • antigens/peptides/epitopes
  • autoimmune
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Identity

International Standard Serial Number (ISSN)

  • 0014-2980

Digital Object Identifier (DOI)

  • 10.1002/eji.200737703

PubMed ID

  • 18395850
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Additional Document Info

start page

  • 968

end page

  • 976

volume

  • 38

issue

  • 4

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