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腺病毒六邻体蛋白上保守的细胞毒性T淋巴细胞表位可扩增亚组交叉反应性和亚组特异性CD8⁺T细胞。

Conserved CTL epitopes on the adenovirus hexon protein expand subgroup cross-reactive and subgroup-specific CD8+ T cells.

作者信息

Leen Ann M, Sili Uluhan, Vanin Elio F, Jewell Alan M, Xie Weidong, Vignali Dario, Piedra Pedro A, Brenner Malcolm K, Rooney Cliona M

机构信息

Center for Cell and Gene Therapy, Department of Pediatrics, 6621 Fannin St, MC 3-3320, Houston, TX, USA.

出版信息

Blood. 2004 Oct 15;104(8):2432-40. doi: 10.1182/blood-2004-02-0646. Epub 2004 Jul 20.

Abstract

Adenoviruses often cause lethal infections in immunocompromised individuals. Adoptive transfer of immune T cells offers a therapeutic option, but this strategy has been hindered by the paucity of information on molecular targets of cellular immunity and by the immunologic heterogeneity of the 51 human adenoviruses, which are grouped from A to F on the basis of genome size, composition, homology, and organization. Clonal analysis of the adenovirus-specific cytotoxic T lymphocyte (CTL) responses of seropositive individuals identified 5 novel CD8(+) T-cell epitopes, all located in conserved regions of the capsid protein hexon. Reactive T cells were cross-reactive between 2 to 4 groups, while no T cells specific for a single subgroup were detected. Thus, by exploiting these peptide targets, it is possible to prepare a T-cell population capable of reacting with most adenoviruses that cause disease in immunocompromised patients.

摘要

腺病毒常常在免疫功能低下的个体中引发致命感染。免疫T细胞的过继转移提供了一种治疗选择,但这一策略受到细胞免疫分子靶点信息匮乏以及51种人类腺病毒免疫异质性的阻碍,这些腺病毒根据基因组大小、组成、同源性和结构从A组到F组进行分类。对血清反应阳性个体的腺病毒特异性细胞毒性T淋巴细胞(CTL)反应进行克隆分析,确定了5个新的CD8(+) T细胞表位,均位于衣壳蛋白六邻体的保守区域。反应性T细胞在2至4个组之间具有交叉反应性,而未检测到对单个亚组具有特异性的T细胞。因此,通过利用这些肽靶点,有可能制备出能够与大多数在免疫功能低下患者中致病的腺病毒发生反应的T细胞群体。

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