Identification of novel IGRP epitopes targeted in type 1 diabetes patients

Clin Immunol. 2008 Jun;127(3):359-65. doi: 10.1016/j.clim.2008.01.015. Epub 2008 Mar 20.


CD8(+) T cells play an important role in the development of type 1 diabetes (T1D) in NOD mice and humans. IGRP (islet-specific glucose-6-phosphatase catalytic subunit-related protein) has emerged in recent years as a major antigen in NOD mice. Therefore, we aimed to determine if IGRP is an antigen in T1D patients and to identify the HLA-A2-restricted IGRP epitopes targeted. Using IFN-gamma ELISPOT assay, we tested PBMC from recent-onset pediatric T1D patients and healthy controls for reactivity to four IGRP peptides directly ex vivo. Importantly, 65% of patients and 0% of controls were positive for at least one IGRP peptide. Two of these have not been reported previously. These data provide evidence that IGRP is a CD8(+) T cell antigen in humans, contributing to the understanding of the underlying disease process as well as to future directions for diagnosis and monitoring disease progression in T1D patients.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Autoantigens / immunology*
  • CD8-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / metabolism
  • Child
  • Diabetes Mellitus, Type 1 / blood
  • Diabetes Mellitus, Type 1 / immunology*
  • Epitope Mapping
  • Epitopes / immunology*
  • Female
  • Glucose-6-Phosphatase / immunology*
  • HLA-A2 Antigen / immunology*
  • HLA-A2 Antigen / metabolism
  • Humans
  • Interferon-gamma / biosynthesis
  • Interferon-gamma / immunology
  • Islets of Langerhans / immunology
  • Male
  • Peptides / immunology
  • Peptides / metabolism


  • Autoantigens
  • Epitopes
  • HLA-A2 Antigen
  • Peptides
  • Interferon-gamma
  • Glucose-6-Phosphatase
  • G6PC2 protein, human