Restricted islet-cell reactive T cell repertoire of early pancreatic islet infiltrates in NOD mice
Restricted islet-cell reactive T cell repertoire of early pancreatic islet infiltrates in NOD mice
复制标题
DOI：
10.1073/pnas.142284899
复制
发表时间：
2002-07-09
影响因子：
11.1
通讯作者：
Davis, MM
中科院分区：
文献类型：
--
作者：
Baker, FJ;Lee, M;Davis, MM
引发自身免疫性糖尿病的机制尚不清楚。在这里，我们描述了一种在非肥胖糖尿病小鼠（NOD）疾病早期阶段从单个胰岛浸润T细胞中识别T细胞受体(TCR) α链和β链的方法。对这些早期胰岛浸润的TCR库的分析揭示了一小部分TCR序列的富集。这些TCR的体外重建表明，这些受体赋予胰岛细胞反应性，而不是对特性良好的自身抗原、谷氨酸脱羧酶（GAD65）和胰岛素的反应性。因此，NOD的自身免疫性糖尿病可能由不同于GAD65和胰岛素的有限抗原引发。
The mechanisms responsible for initiating autoimmune diabetes remain obscure. Here, we describe a method for identifying both the alpha- and beta-chains of the T cell receptor (TCR) from individual pancreatic islet-infiltrating T cells at the earliest stages of disease in nonobese diabetic mice (NOD). Analysis of the TCR repertoire of these early islet infiltrates reveals enrichment for a small subset of TCR sequences. Reconstitution of these TCR in vitro demonstrates that these receptors confer reactivity to islet cells but not to the well characterized autoantigens, glutamic acid decarboxylase (GAD65) and insulin. Thus, autoimmune diabetes in NOD may be initiated by a limited number of antigens distinct from GAD65 and insulin.