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T细胞识别的脊髓灰质炎病毒抗原序列:利用CD4 + T细胞克隆确定的VP1和VP3上的血清型特异性表位以及VP4上的交叉反应表位

Antigenic sequences of poliovirus recognized by T cells: serotype-specific epitopes on VP1 and VP3 and cross-reactive epitopes on VP4 defined by using CD4+ T-cell clones.

作者信息

Mahon B P, Katrak K, Mills K H

机构信息

Division of Immunobiology, National Institute for Biological Standards and Control, Potters Bar, Hertfordshire, United Kingdom.

出版信息

J Virol. 1992 Dec;66(12):7012-20. doi: 10.1128/JVI.66.12.7012-7020.1992.

Abstract

A panel of poliovirus-specific murine CD4+ T-cell clones has been established from both BALB/c (H-2d) and CBA (H-2k) mice immunized with Sabin vaccine strains of poliovirus serotype 1, 2, or 3. T-cell clones were found to be either serotype specific or cross-reactive between two or all three serotypes. Specificity analysis against purified poliovirus proteins demonstrated that T-cell clones recognized determinants on the surface capsid proteins VP1, VP2, and VP3 and the internal capsid protein VP4. Panels of overlapping synthetic peptides were used to identify eight distinct T-cell epitopes. One type 3-specific T-cell clone recognized an epitope within amino acids 257 and 264 of VP1. Three T-cell epitopes corresponding to residues 14 to 28, 189 to 203, and 196 to 210 were identified on VP3 of poliovirus type 2. The remaining four T-cell epitopes were mapped to an immunodominant region of VP4, encompassed within residues 6 and 35 and recognized by both H-2d and H-2k mice. The epitopes on VP4 were conserved between serotypes, and this may account for the predominantly cross-reactive poliovirus-specific T-cell response observed with polyclonal T-cell populations. In contrast, T-cell clones that recognize epitopes on VP1 or VP3 were largely serotype specific; single or multiple amino acid substitutions were found to be critical for T-cell recognition.

摘要

用脊髓灰质炎病毒1、2或3型的萨宾疫苗株免疫BALB/c(H-2d)和CBA(H-2k)小鼠后,已建立了一组脊髓灰质炎病毒特异性的小鼠CD4+T细胞克隆。发现T细胞克隆要么是血清型特异性的,要么在两种或所有三种血清型之间具有交叉反应性。针对纯化的脊髓灰质炎病毒蛋白的特异性分析表明,T细胞克隆识别表面衣壳蛋白VP1、VP2和VP3以及内部衣壳蛋白VP4上的决定簇。使用重叠合成肽组来鉴定八个不同的T细胞表位。一个3型特异性T细胞克隆识别VP1氨基酸257至264内的一个表位。在脊髓灰质炎病毒2型的VP3上鉴定出对应于残基14至28、189至203和196至210的三个T细胞表位。其余四个T细胞表位定位于VP4的一个免疫显性区域,该区域包含在残基6和35内,并且被H-2d和H-2k小鼠识别。VP4上的表位在血清型之间是保守的,这可能解释了用多克隆T细胞群体观察到的主要交叉反应性脊髓灰质炎病毒特异性T细胞反应。相比之下,识别VP1或VP3上表位的T细胞克隆在很大程度上是血清型特异性的;发现单个或多个氨基酸取代对T细胞识别至关重要。

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