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Diabetogenic T-cell clones recognize an altered peptide of chromogranin A

Thomas Delong1, Rocky L Baker, Jing He

  • 1Denver School of Medicine and National Jewish Health, Denver, Colorado, USA.

Diabetes
|August 23, 2012
PubMed

Insights

Post-translational modification by transglutaminase (TGase) enhances the antigenicity of Chromogranin A (ChgA) peptide WE14. This modification significantly boosts T-cell responses, suggesting a key role in type 1 diabetes pathogenesis.

Area of Science:

  • Immunology
  • Endocrinology
  • Biochemistry

Background:

  • Chromogranin A (ChgA) is an antigen target for diabetogenic CD4 T-cell clones.
  • T-cell clones, like BDC-2.5, show weak responses to the ChgA-derived peptide WE14.

Purpose of the Study:

  • To investigate the effect of transglutaminase (TGase) on the antigenicity of the WE14 peptide.
  • To determine if TGase modification enhances T-cell recognition of WE14 in the context of type 1 diabetes.

Main Methods:

  • Treatment of the WE14 peptide with TGase.
  • Assessing T-cell responses using NOD-derived CD4 T-cell clones and BDC-2.5 TCR transgenic mice.
  • Evaluating responses of primary CD4 T cells from NOD mice.

Main Results:

  • TGase treatment converts WE14 into a highly antigenic T-cell epitope.
  • Responses of multiple NOD-derived CD4 T-cell clones and BDC-2.5 T cells were significantly increased after TGase conversion.
  • Primary NOD CD4 T cells responded to lower concentrations of TGase-treated WE14 compared to native WE14.

Conclusions:

  • Post-translational modification, specifically by TGase, critically influences the generation of T-cell epitopes.
  • This modification may play a significant role in the development of type 1 diabetes.

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