Clonotypic structure of the human CD4+ memory T cell response to cytomegalovirus
Clonotypic structure of the human CD4+ memory T cell response to cytomegalovirus
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DOI：
10.4049/jimmunol.167.3.1151
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发表时间：
2001-08-01
影响因子：
4.4
通讯作者：
Picker, LJ
中科院分区：
文献类型：
--
作者：
Bitmansour, AD;Waldrop, SL;Picker, LJ
CMV特异性CD 4（+）记忆T细胞的高稳态频率在CMV暴露的受试者中维持，并且这些细胞被认为在这种永久性感染的免疫控制中起关键作用。然而，这一对策的基本组成部分没有得到明确界定。在这里，我们报告了使用流式细胞术和分子技术的逐步应用，以确定在新鲜获得的CMV特异性CD 4（+）记忆T细胞群的四个健康的CMV暴露的人类受试者的TCR V β定义的克隆型的数量和大小。该分析揭示了一个稳定的克隆型层次结构，其中1-3个显性克隆型与更多的亚显性和次要克隆型保持一致。这些占优势的克隆型占总体CMV应答的10-50%，并占外周血CD 4（+）T细胞的0.3 - 4.0%。两名受试者表现出免疫显性反应的CMV基质磷蛋白pp 65内的单表位，这些单表位反应介导的一个单一的显性克隆型在一个主题，和多个亚显性和次要克隆型在其他。因此，正常受试者中CMV特异性CD 4（+）T细胞记忆库的特征在于显著的克隆型优势和表位集中的潜力，这表明针对CMV再激活的免疫监视的主要责任在于少数克隆识别有限的CMV决定簇。这些数据具有重要的意义，了解遗传稳定的慢性病毒病原体，如CMV的控制机制，并提供可能的洞察失败的遗传灵活的病原体，如HIV-1。
High steady-state frequencies of CMV-specific CD4(+) memory T cells are maintained in CMV-exposed subjects, and these cells are thought to play a key role in the immunologic control of this permanent infection. However, the essential components of this response are poorly defined. Here, we report the use of a step-wise application of flow cytometric and molecular techniques to determine the number and size of the TCR V beta -defined clonotypes within freshly obtained CMV-specific CD4(+) memory T cell populations of four healthy, CMV-exposed human subjects. This analysis revealed a stable clonotypic hierarchy in which 1-3 dominant clonotypes are maintained in concert with more numerous subdominant and minor clonotypes. These dominant clonotypes accounted for 10-50% of the overall CMV response, and comprised from 0.3 to 4.0% of peripheral blood CD4(+) T cells. Two subjects displayed immunodominant responses to single epitopes within the CMV matrix phosphoprotein pp65; these single epitope responses were mediated by a single dominant clonotype in one subject, and by multiple subdominant and minor clonotypes in the other. Thus, the CMV-specific CD4(+) T cell memory repertoire in normal subjects is characterized by striking clonotypic dominance and the potential for epitope focusing, suggesting that primary responsibility for immunosurveillance against CMV reactivation rests with a handful of clones recognizing a limited array of CMV determinants. These data have important implications for the understanding of mechanisms by which a genetically stable chronic viral pathogen such as CMV is controlled, and offer possible insight into the failure of such control for a genetically flexible pathogen like HIV-1.