NOD小鼠早期胰岛浸润中受限制的胰岛细胞反应性T细胞库。
Restricted islet-cell reactive T cell repertoire of early pancreatic islet infiltrates in NOD mice.
作者信息
Baker Felix J, Lee Mark, Chien Yueh-hsiu, Davis Mark M
机构信息
Howard Hughes Medical Institute and Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305, USA.
出版信息
Proc Natl Acad Sci U S A. 2002 Jul 9;99(14):9374-9. doi: 10.1073/pnas.142284899. Epub 2002 Jun 24.
Abstract
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.
摘要
引发自身免疫性糖尿病的机制仍不清楚。在此，我们描述了一种方法，可在非肥胖糖尿病小鼠（NOD）疾病的最早阶段，从单个胰岛浸润性T细胞中鉴定T细胞受体（TCR）的α链和β链。对这些早期胰岛浸润细胞的TCR库分析显示，一小部分TCR序列得到富集。在体外重建这些TCR表明，这些受体赋予对胰岛细胞的反应性，但对特征明确的自身抗原谷氨酸脱羧酶（GAD65）和胰岛素无反应性。因此，NOD中的自身免疫性糖尿病可能由有限数量的不同于GAD65和胰岛素的抗原引发。
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