Identification of the beta cell antigen targeted by a prevalent population of pathogenic CD8+ T cells in autoimmune diabetes.
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.
Lieberman
Scott M
SM
Department of Microbiology and Immunology, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461, USA.
Evans
Anne M
AM
Han
Bingye
B
Takaki
Toshiyuki
T
Vinnitskaya
Yuliya
Y
Caldwell
Jennifer A
JA
Serreze
David V
DV
Shabanowitz
Jeffrey
J
Hunt
Donald F
DF
Nathenson
Stanley G
SG
Santamaria
Pere
P
DiLorenzo
Teresa P
TP
D000818:Animals; D001324:Autoantigens / Q000235:genetics / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D019556:COS Cells; D002522:Chlorocebus aethiops; D002846:Chromatography, Affinity; D002999:Clone Cells / Q000276:immunology; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology*; D004195:Disease Models, Animal; D019673:Genes, T-Cell Receptor alpha; D019674:Genes, T-Cell Receptor beta; D005952:Glucose-6-Phosphatase; D006183:H-2 Antigens / Q000276:immunology; D007515:Islets of Langerhans / Q000276:immunology*; D008213:Lymphocyte Activation; D051379:Mice; D016688:Mice, Inbred NOD; D008822:Mice, Transgenic; D010446:Peptide Fragments / Q000276:immunology; D011506:Proteins / Q000235:genetics / Q000276:immunology*; D013047:Specific Pathogen-Free Organisms; D014162:Transfection
D001324:Autoantigens; D006183:H-2 Antigens; C024755:H-2K(K) antigen; D010446:Peptide Fragments; D011506:Proteins; D005952:Glucose-6-Phosphatase; C492194:G6PC2 protein, human; C117983:G6pc2 protein, mouse