Identification of the β cell antigen targeted by a prevalent population of pathogenic CD8+ T cells in autoimmune diabetes

被引:320
作者
Lieberman, SM
Evans, AM
Han, BY
Takaki, T
Vinnitskaya, Y
Caldwell, JA
Serreze, DV
Shabanowitz, J
Hunt, DF
Nathenson, SG
Santamaria, P
DiLorenzo, TP
机构
[1] Yeshiva Univ Albert Einstein Coll Med, Dept Microbiol & Immunol, Bronx, NY 10461 USA
[2] Yeshiva Univ Albert Einstein Coll Med, Dept Cell Biol, Bronx, NY 10461 USA
[3] Yeshiva Univ Albert Einstein Coll Med, Dept Med, Div Endocrinol, Bronx, NY 10461 USA
[4] Univ Virginia, Dept Chem, Charlottesville, VA 22904 USA
[5] Univ Virginia, Dept Pathol, Charlottesville, VA 22904 USA
[6] Univ Calgary, Hlth Sci Ctr, Dept Microbiol & Infect Dis, Calgary, AB T2N 4N1, Canada
[7] Univ Calgary, Hlth Sci Ctr, Julia McFarlane Diabet Res Ctr, Calgary, AB T2N 4N1, Canada
[8] Jackson Lab, Bar Harbor, ME 04609 USA
关键词
D O I
10.1073/pnas.0932778100
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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 13 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.
引用
收藏
页码:8384 / 8388
页数:5
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