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针对复杂抗原的T细胞应答的表位分析:对人鼻病毒衣壳的增殖应答。

Epitope analysis of the T cell response to a complex antigen: proliferative responses to human rhinovirus capsids.

作者信息

Hastings G Z, Francis M J, Rowlands D J, Chain B M

机构信息

Department of Biology, University College, London, GB.

出版信息

Eur J Immunol. 1993 Sep;23(9):2300-5. doi: 10.1002/eji.1830230937.

DOI:10.1002/eji.1830230937
PMID:7690329
Abstract

Understanding the factors which regulate the repertoire of a T cell response is important when selecting T helper cell epitopes for inclusion in synthetic viral vaccines. In this study we have examined the T cell response to human rhinovirus (HRV) type 1 A in a mouse model system, using a comprehensive set of synthetic peptides which span all four of the proteins which make up the HRV capsid. This constitutes the first study to use a set of peptides covering the entire sequence of all structural proteins of any virus. This study identifies the major proliferative (CD4) T cell epitopes within the minor receptor group HRV 1 A, and analyzes these epitopes with relation to their location within the three-dimensional structure of the virus. The proliferative response to HRV is highly selective, with strong responses to only a very small number of epitopes, many of which are grouped together within restricted areas of the primary structure of the HRV proteins. The repertoire of the response is almost entirely specific to the major histocompatibility complex haplotype of the host. The major T cell epitopes are spatially distinct from the sites of the major antibody recognition sites, and are buried within the viral capsid. In striking contrast to the antibody responses, the T cell responses are highly cross-reactive against a wide variety of viral serotypes.

摘要

在选择用于合成病毒疫苗的T辅助细胞表位时,了解调节T细胞反应库的因素非常重要。在本研究中,我们使用了一组涵盖构成人鼻病毒(HRV)衣壳的所有四种蛋白质的合成肽,在小鼠模型系统中研究了对1A 型人鼻病毒(HRV)的T细胞反应。这是第一项使用一组覆盖任何病毒所有结构蛋白完整序列的肽的研究。本研究确定了次要受体组HRV 1A内的主要增殖性(CD4)T细胞表位,并根据它们在病毒三维结构中的位置对这些表位进行了分析。对HRV的增殖反应具有高度选择性,仅对极少数表位有强烈反应,其中许多表位在HRV蛋白一级结构的受限区域内聚集在一起。反应库几乎完全针对宿主的主要组织相容性复合体单倍型。主要T细胞表位在空间上与主要抗体识别位点不同,并且埋藏在病毒衣壳内。与抗体反应形成鲜明对比的是,T细胞反应对多种病毒血清型具有高度交叉反应性。

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