ZnT8 Is a Major CD8+ T Cell–Recognized Autoantigen in Pediatric Type 1 Diabetes

2012/05/15 by Emmanuelle Énée, Émmanuelle Énée, Roland Kratzer +13 · 23 citations
Biochemistry, Genetics and Molecular Biology · Immunology and Microbiology · Medicine · #Antibody #Antigen #Autoantibody #CD8 #Diabetes and associated disorders #Diabetes mellitus #ELISPOT #Endocrinology #Epitope #Human leukocyte antigen #Immune Cell Function and Interaction #Immune system #Immunology #Medicine #Population #T cell #T-cell and B-cell Immunology #Type 1 diabetes

paper · pdf · doi:10.2337/db12-0071

openalex publication_date 2012/05/15 · openalex created_date 2025/10/10 · openalex updated_date 2026/07/31

Abstract

Type 1 diabetes results from the destruction of β-cells by an autoimmune T-cell response assisted by antigen-presenting B cells producing autoantibodies. CD8(+) T-cell responses against islet cell antigens, thought to play a central role in diabetes pathogenesis, can be monitored using enzyme-linked immunosorbent spot (ELISpot) assays. However, such assays have been applied to monitoring of adult patients only, leaving aside the large and increasing pediatric patient population. The objective of this study was twofold: 1) to develop a CD8(+) T-cell interferon-γ ELISpot assay for pediatric patients and 2) to determine whether zinc transporter 8 (ZnT8), a recently described target of autoantibodies in a majority of patients, is also recognized by autoreactive CD8(+) T cells. Using DNA immunization of humanized mice, we identified nine HLA-A2-restricted ZnT8 epitopes. Among 36 HLA-A2(+) children with diabetes, 29 responded to ZnT8 epitopes, whereas only 3 of 16 HLA-A2(+) control patients and 0 of 17 HLA-A2(-) control patients responded. Some single ZnT8 epitopes performed as well as the group of epitopes in discriminating between patients and control individuals. Thus, ZnT8 is a major CD8(+) T-cell autoantigen, and ELISpot assays display similar performance in adult and pediatric type 1 diabetes.

Cited by

• Cellular zinc metabolism and zinc signaling: from biological functions to diseases and therapeutic targets
• Comparison of autoantibody-positive and autoantibody-negative pediatric participants enrolled in the T1D Exchange clinic registry. [europepmc]
• Proteome-wide survey of the autoimmune target repertoire in autoimmune polyendocrine syndrome type 1. [europepmc]
• Identification of Candidate Tolerogenic CD8(+) T Cell Epitopes for Therapy of Type 1 Diabetes in the NOD Mouse Model. [europepmc]
• Beta cell antigens in type 1 diabetes: triggers in pathogenesis and therapeutic targets. [europepmc]
• CD8 + T cells specific for the islet autoantigen IGRP are restricted in their T cell receptor chain usage. [europepmc]
• Autoreactive T cells in type 1 diabetes. [europepmc]
• A subclass of serum anti-ZnT8 antibodies directed to the surface of live pancreatic β-cells. [europepmc]
• T Cell-Mediated Beta Cell Destruction: Autoimmunity and Alloimmunity in the Context of Type 1 Diabetes. [europepmc]
• Islet-reactive CD8 + T cell frequencies in the pancreas, but not in blood, distinguish type 1 diabetic patients from healthy donors. [europepmc]
• Identification and Analysis of Islet Antigen-Specific CD8 + T Cells with T Cell Libraries. [europepmc]
• Therapies to Suppress β Cell Autoimmunity in Type 1 Diabetes. [europepmc]
• Standardizing T-Cell Biomarkers in Type 1 Diabetes: Challenges and Recent Advances. [europepmc]
• What has zinc transporter 8 autoimmunity taught us about type 1 diabetes? [europepmc]
• Down-regulation of the islet-specific zinc transporter-8 (ZnT8) protects human insulinoma cells against inflammatory stress. [europepmc]
• A change in the zinc ion concentration reflects the maturation of insulin-producing cells generated from adipose-derived mesenchymal stem cells. [europepmc]
• Zinc. [europepmc]
• Syngeneically transplanted insulin producing cells differentiated from adipose derived stem cells undergo delayed damage by autoimmune responses in NOD mice. [europepmc]
• HERV-K Envelope Protein Induces Long-Lasting Production of Autoantibodies in T1DM Patients at Onset in Comparison to ZNT8 Autoantibodies. [europepmc]
• Cellular zinc metabolism and zinc signaling: from biological functions to diseases and therapeutic targets. [europepmc]
• The role of islet autoantigen-specific T cells in the onset and treatment of type 1 diabetes mellitus. [europepmc]
• Screening of Diabetes-Associated Autoantigens and Serum Antibody Profiles Using a Phage Display System. [europepmc]
• A Compound Screen Based on Isogenic hESC-Derived β Cell Reveals an Inhibitor Targeting ZnT8-Mediated Zinc Transportation to Protect Pancreatic β Cell from Stress-Induced Cell Death. [europepmc]

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