TY - JOUR
T1 - Identification of the β cell antigen targeted by a prevalent population of pathogenic CD8+ T cells in autoimmune diabetes
AU - Lieberman, Scott M.
AU - Evans, Anne M.
AU - Han, Bingye
AU - Takaki, Toshiyuki
AU - Vinnitskaya, Yuliya
AU - Caldwell, Jennifer A.
AU - Serreze, David V.
AU - Shabanowitz, Jeffrey
AU - Hunt, Donald F.
AU - Nathenson, Stanley G.
AU - Santamaria, Pere
AU - DiLorenzo, Teresa P.
PY - 2003/7/8
Y1 - 2003/7/8
N2 - Type 1 diabetes is an autoimmune disease in which autoreactive T cells attack and destroy the insulin-producing pancreatic β cells. CD8+ T cells are essential for this β 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.
AB - Type 1 diabetes is an autoimmune disease in which autoreactive T cells attack and destroy the insulin-producing pancreatic β cells. CD8+ T cells are essential for this β 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.
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U2 - 10.1073/pnas.0932778100
DO - 10.1073/pnas.0932778100
M3 - Article
C2 - 12815107
AN - SCOPUS:0037478632
SN - 0027-8424
VL - 100
SP - 8384
EP - 8388
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 14
ER -