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Immunogenetics

, Volume 46, Issue 1, pp 29–34 | Cite as

Identification of immunogenic epitopes of GAD 65 presented by A  g7 in non-obese diabetic mice

  • Cheng-Chi Chao
  • Hugh. O. McDevitt
ORIGINAL PAPER

Abstract

 The autoantigen glutamic acid decarboxylase 65 (GAD 65) is believed to be an important target antigen in insulin-dependent diabetes mellitus (IDDM), since an age-related spontaneous breakdown in tolerance is observed, and cell-mediated and autoantibody immune responses have been reported in humans and NOD mice. We sought to identify immunogenic epitopes of GAD 65 which are presented to T cells by the type I diabetes susceptibility allele (A g7 ), using overlapping 15-mer synthetic peptides spanning the entire sequence of this protein. Four epitopes (p206 – 220, p221 – 235, p286 – 300, p571 – 585) were identified by screening a panel of T-cell hybridomas generated from GAD 65-immunized NOD mice. These immunogenic epitopes are unrelated to the previously described T-cell epitopes of GAD 65 reported in NOD mice. Of the GAD 65 amino acid sequence, 206 – 220 and 221 – 235 are the two most dominant T-cell epitopes identified in this study. Sixty-three percent and 25% of GAD 65-responding T cell hybridomas react to p206 – 220 and p221 – 235, respectively. The remaining two peptides (p286 – 300, p571 – 585) are less dominant T-cell responses. The identification of the whole spectrum of GAD 65 Ag7 epitopes should further the investigation of the role of this autoantigen in the pathogenesis of IDDM.

Keywords

Glutamic Acid Diabetic Mouse Glutamic Acid Decarboxylase Susceptibility Allele Diabetes Susceptibility 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Springer-Verlag Berlin Heidelberg 1997

Authors and Affiliations

  • Cheng-Chi Chao
    • 1
  • Hugh. O. McDevitt
    • 1
  1. 1.Departments of Microbiology and Immunology, and Medicine, Sherman Fairchild Building, Room D345, Stanford University Medical Center, Stanford, California 94305, USAUS

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