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* Immuno-Endocrinology Unité Mixte de Recherche 707, Institut National de la Recherche Agronomique/Ecole Nationale Vétérinaire de Nantes/Université, Nantes, France;
Institut National de la Santé et de la Recherche Médicale, Unité 580, Paris, France;
Université Paris Descartes, Paris, France;
Clinique d’Endocrinologie, Hôpital Hôtel-Dieu, Nantes, France; and
¶ Department of Internal Medicine, University of Turin, Turin, Italy
Type 1 diabetes (T1D) results from the autoimmune destruction of pancreatic 
cells. CD8+ T cells have recently been assigned a major role in cell injury. Consequently, the identification of autoreactive CD8+ T cells in humans remains essential for development of therapeutic strategies and of assays to identify aggressive cells. However, this identification is laborious and limited by quantities of human blood samples available. We propose a rapid and reliable method to identify autoantigen-derived epitopes recognized by human CD8+ T lymphocytes in T1D patients. Human histocompatibility leukocyte Ags-A*0201 (HLA-A*0201) transgenic mice were immunized with plasmids encoding the T1D-associated autoantigens: 65 kDa glutamic acid decarboxylase (GAD) or insulinoma-associated protein 2 (IA-2). Candidate epitopes for T1D were selected from peptide libraries by testing the CD8+ reactivity of vaccinated mice. All of the nine-candidate epitopes (five for GAD and four for IA-2) identified by our experimental approach were specifically recognized by CD8+ T cells from newly diagnosed T1D patients (n = 19) but not from CD8+ T cells of healthy controls (n = 20). Among these, GAD114–123, GAD536–545 and IA-2805–813 were recognized by 53%, 25%, and 42% of T1D patients, respectively.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This study was supported by the Association de Langue Française pour l’Etude du Diabéte et des maladies Métaboliques and the Juvenile Diabetes Research Foundation Grant 1-2005-39.
2 Address correspondence and reprint requests to Drs. Philippe Blancou and Jean-Marie Bach, Unité Mixte de Recherche 707, Immuno-Endocrinology Unit, Ecole Nationale Vétérinaire de Nantes, BP 40706, Nantes, France. E-mail addresses: blancou{at}vet-nantes.fr and bach{at}vet-nantes.fr
3 Abbreviations used in this paper: T1D, type 1 diabetes; GAD, glutamic acid decarboxylase; IA-2, insulinoma-associated protein 2; IGRP, islet-specific glucose-6-phosphatase.
This article has been cited by other articles:
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  E. Martinuzzi, G. Novelli, M. Scotto, P. Blancou, J.-M. Bach, L. Chaillous, G. Bruno, L. Chatenoud, P. van Endert, and R. Mallone The Frequency and Immunodominance of Islet-Specific CD8+ T-cell Responses Change after Type 1 Diabetes Diagnosis and Treatment Diabetes, May 1, 2008; 57(5): 1312 - 1320. [Abstract] [Full Text] [PDF]
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 E. Enee, E. Martinuzzi, P. Blancou, J.-M. Bach, R. Mallone, and P. van Endert Equivalent Specificity of Peripheral Blood and Islet-Infiltrating CD8+ T Lymphocytes in Spontaneously Diabetic HLA-A2 Transgenic NOD Mice J. Immunol., April 15, 2008; 180(8): 5430 - 5438. [Abstract] [Full Text] [PDF]
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