Identification of the β cell antigen targeted by a prevalent population of pathogenic CD8+ T cells in autoimmune diabetes
Identification of the β cell antigen targeted by a prevalent population of pathogenic CD8+ T cells in autoimmune diabetes
复制标题
DOI：
10.1073/pnas.0932778100
复制
发表时间：
2003-07-08
影响因子：
11.1
通讯作者：
DiLorenzo, TP
中科院分区：
文献类型：
--
作者：
Lieberman, SM;Evans, AM;DiLorenzo, TP
1型糖尿病是一种自身免疫性疾病，其中自身反应性T细胞攻击并破坏产生胰岛素的胰腺β细胞。CD8(+) T细胞对这13种细胞的破坏至关重要，但它们的特异性抗原靶点在很大程度上是未知的。在这里，我们揭示了非肥胖糖尿病小鼠中普遍存在的致病性CD8(+) T细胞群靶向的自身抗原是胰岛特异性葡萄糖-6-磷酸酶催化亚基相关蛋白（IGRP）。通过四聚体技术，可以在胰岛和外周血中直接检测到igrp反应性T细胞。人类IGRP基因定位于糖尿病易感位点，表明IGRP也可能是人类1型糖尿病致病性T细胞的抗原，因此是诊断和治疗方法的一个新的潜在靶点。
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.