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Proc Natl Acad Sci U S A. 2003 Jul 22;100(15):8626-8.
Identification of the beta cell antigen targeted by a prevalent population of pathogenic CD8+ T cells in autoimmune diabetes.
Lieberman SM,
Evans AM,
Han B,
Takaki T,
Vinnitskaya Y,
Caldwell JA,
Serreze DV,
Shabanowitz J,
Hunt DF,
Nathenson SG,
Santamaria P,
DiLorenzo TP.
Department of Microbiology and Immunology, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461, USA.
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.
PMID: 12815107 [PubMed - indexed for MEDLINE]
PMCID: PMC166238