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T cell cross-reactivity between coxsackievirus and glutamate decarboxylase is associated with a murine diabetes susceptibility allele.
柯萨奇病毒和谷氨酸脱羧酶之间的 T 细胞交叉反应性与小鼠糖尿病易感性等位基因相关。

摘要

Limited regions of amino acid sequence similarity frequently occur between microbial antigens and host proteins. It has been widely anticipated that during infection such sequence similarities could induce cross-reactive T cell responses, thereby initiating T cell-mediated autoimmune disease. However, the nature of major histocompatibility complex (MHC)-restricted antigen presentation confers a number of constraints that should make this type of T cell cross-reactivity a rare, MHC allele-dependent event. We tested this prediction using two insulin-dependent diabetes mellitus (IDDM)-associated antigens, coxsackievirus P2-C (Cox P2-C) protein and glutamate decarboxylase (GAD65), which share a prototypic sequence similarity of six consecutive amino acids within otherwise unrelated proteins. We surveyed a panel of 10 murine MHC class II alleles that encompass the spectrum of standard alleles for the ability to cross-reactively present Cox P2-C and GAD65. Out of the 10 restriction elements tested, the sequence similarity regions were both dominant determinants and were cross-reactively displayed after the natural processing of whole antigens, only in the context of I-Anod. These data show that cross-reactive T cell recognition of sequence similarity regions in unrelated proteins is confined to certain MHC alleles, which may explain MHC association with autoimmune disease. It is striking that these two diabetes-associated antigens were cross-reactively recognized only in the context of a diabetes susceptibility allele. Since the human and the murine class II alleles associated with IDDM share conserved features, cross-reactive T cell recognition of GAD65 and Cox P2-C may contribute to the pathogenesis of human IDDM and account for the epidemiological association of coxsackievirus with IDDM.

译文

微生物抗原和宿主蛋白之间经常出现有限的氨基酸序列相似性区域。人们普遍预期,在感染期间,这种序列相似性可以诱导交叉反应性 T 细胞反应,从而引发 T 细胞介导的自身免疫性疾病。然而,主要组织相容性复合体 (MHC) 限制性抗原呈递的性质赋予了许多限制,这些限制应该使这种类型的 T 细胞交叉反应成为一种罕见的 MHC 等位基因依赖事件。我们使用两种胰岛素依赖性糖尿病 (IDDM) 相关抗原,柯萨奇病毒 P2-C (Cox P2-C) 蛋白和谷氨酸脱羧酶 (GAD65) 测试了这一预测, 它们在其他不相关的蛋白质中共享六个连续氨基酸的原型序列相似性。我们调查了一组 10 只小鼠 MHC II 类等位基因,这些等位基因包含了标准等位基因的光谱,用于交叉反应呈现 Cox P2-C 和 gad65 的能力。在测试的 10 个限制性元件中,序列相似区域都是主要的决定因素,并且在整个抗原的自然加工后交叉反应显示,仅在 I-Anod 的背景下。这些数据表明,不相关蛋白质中序列相似区域的交叉反应 T 细胞识别仅限于某些 MHC 等位基因,这可能解释 MHC 与自身免疫性疾病的关联。引人注目的是,这两种糖尿病相关抗原仅在糖尿病易感性等位基因的背景下被交叉反应识别。由于人类和小鼠与 IDDM 相关的 II 类等位基因具有保守特征, GAD65 和 Cox P2-C 的交叉反应 T 细胞识别可能有助于人类 IDDM 的发病机制,并解释柯萨奇病毒与 IDDM 的流行病学关联。

Glutamate decarboxylase

内分泌 细胞因子 临床研究术语
概述  :  

谷氨酸脱羧酶是一种催化谷氨酸脱羧为GABA和CO2的酶。在哺乳动物中,GAD 以分子量分别为67kDa和65kDa的两种同工型存在(GAD67和GAD65),它们由不同染色体上的两个不同基因(分别为GAD1和GAD2基因,第4和10号染色体)编码。GAD 67和GAD 65在GABA用作大脑中表达的神经递质,这两种酶,维持哺乳动物GABA的主要生理供应,在发育中的大脑中可以检测到GAD 67的几种截短的转录本和多肽,但是它们的功能是未知的。 在神

Glutamate   英 /'gluːtəmeɪt/   美 /'ɡlʊtə,met/

释    义   n. [生化] 谷氨酸盐;[生化] 谷氨酸酯

例    句   Food additives like salt and monosodium glutamate also are suspected causes. 诸如盐和味精之类的食品添加剂也被认为是原因。

 

Decarboxylase   英 /,dikɑr'bɑksə,les; ,dikɑr'bɑksə,lez/

释    义   n. [生化] 脱羧酶(等于carboxylase)

例    句   Tyrosine decarboxylase is closely related to tyramine production of fermented food.酪氨酸脱羧酶与发酵食品中酪胺的产生密切相关。

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