Identification of the β cell antigen targeted by a prevalent population of pathogenic CD8+T cells in autoimmune diabetes
- 18 June 2003
- journal article
- Published by Proceedings of the National Academy of Sciences in Proceedings of the National Academy of Sciences
- Vol. 100 (14) , 8384-8388
- https://doi.org/10.1073/pnas.0932778100
Abstract
Type 1 diabetes is an autoimmune disease in which autoreactive T cells attack and destroy the insulin-producing pancreatic beta cells. CD8+ T cells are essential for this beta cell destruction, yet their specific antigenic targets are largely unknown. Here, we reveal that the autoantigen targeted by a prevalent population of pathogenic CD8+ T cells in nonobese diabetic mice is islet-specific glucose-6-phosphatase catalytic subunit-related protein (IGRP). Through tetramer technology, IGRP-reactive T cells are readily detected in islets and peripheral blood directly ex vivo. The human IGRP gene maps to a diabetes susceptibility locus, suggesting that IGRP also may be an antigen for pathogenic T cells in human type 1 diabetes and, thus, a new, potential target for diagnostic and therapeutic approaches.Keywords
This publication has 30 references indexed in Scilit:
- Autoreactive CD8 T Cells in Organ-Specific Autoimmunity: Emerging Targets for Therapeutic InterventionImmunity, 2002
- Genetics of type 1 diabetes mellitusGenes & Immunity, 2002
- Analysis of structure and function relationships of an autoantigenic peptide of insulin bound to H-2Kdthat stimulates CD8 T cells in insulin-dependent diabetes mellitusProceedings of the National Academy of Sciences, 2002
- Cloning and Characterization of the Human and Rat Islet-specific Glucose-6-phosphatase Catalytic Subunit-related Protein (IGRP) GenesJournal of Biological Chemistry, 2001
- Insulin-Dependent Diabetes MellitusCell, 1996
- Detection of rare antigen-presenting cells by the lacZ T-cell activation assay suggests an expression cloning strategy for T-cell antigens.Proceedings of the National Academy of Sciences, 1992
- Cloning and Expression of IDDM-Specific Human AutoantigensDiabetes, 1992
- NIT-1, a Pancreatic β-Cell Line Established From a Transgenic NOD/Lt MouseDiabetes, 1991
- Identification of the 64K autoantigen in insulin-dependent diabetes as the GABA-synthesizing enzyme glutamic acid decarboxylaseNature, 1990
- Insulin Antibodies in Insulin-Dependent Diabetics Before Insulin TreatmentScience, 1983