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风疹衣壳蛋白上重叠的CD8 +和CD4 + T细胞表位的特性分析

Characterization of an overlapping CD8+ and CD4+ T-cell epitope on rubella capsid protein.

作者信息

Ou D, Mitchell L A, Décarie D, Gillam S, Tingle A J

机构信息

Faculty of Medicine, University of British Columbia, 950 West 28th Avenue, Vancouver, British Columbia, V5Z 4H4, Canada.

出版信息

Virology. 1997 Sep 1;235(2):286-92. doi: 10.1006/viro.1997.8704.

DOI:10.1006/viro.1997.8704
PMID:9281508
Abstract

A synthetic peptide corresponding to rubella virus capsid protein residues 263 to 275 which contains an epitope recognized by a cloned CD4+ cytotoxic T-lymphocyte (CTL) line was used to induce CD8+ T-cell lines specific to this peptide. A peptide-specific CD8+ CTL clone was derived and characterized. This peptide-specific CD8+ CTL clone exhibited cytotoxicity against target cells infected by a vaccinia recombinant virus expressing rubella virus capsid protein, but not by target cells infected by vaccinia recombinant virus expressing rubella virus E1 or E2 envelope proteins. Analysis of HLA class I restriction of the CD8+ CTL clone revealed that A11 and A3 were restrictive elements. Fine mapping with truncated and overlapping peptide analogs revealed a nonamer sequence, C(264-272), as the T-cell epitope eliciting stronger cytotoxicity. Two anchor residues for binding to HLA A11 and A3 were identified at position 2 (isoleucine) and at position 9 (histidine) or at position 8 (arginine) of the epitope sequence. The identification of overlapping CD4+ and CD8+ T-cell epitopes within the capsid protein sequence C(263-275) implicates a strategy for using such epitopes in a candidate peptide-based rubella vaccine.

摘要

一种对应风疹病毒衣壳蛋白第263至275位残基的合成肽,其包含一个可被克隆的CD4 + 细胞毒性T淋巴细胞(CTL)系识别的表位,被用于诱导针对该肽的CD8 + T细胞系。获得并鉴定了一个肽特异性CD8 + CTL克隆。该肽特异性CD8 + CTL克隆对受表达风疹病毒衣壳蛋白的痘苗重组病毒感染的靶细胞具有细胞毒性,但对受表达风疹病毒E1或E2包膜蛋白的痘苗重组病毒感染的靶细胞没有细胞毒性。对CD8 + CTL克隆的HLA I类限制性分析表明,A11和A3是限制性元件。用截短和重叠的肽类似物进行精细定位,发现一个九聚体序列C(264 - 272)作为引发更强细胞毒性的T细胞表位。在表位序列的第2位(异亮氨酸)和第9位(组氨酸)或第8位(精氨酸)鉴定出两个与HLA A11和A3结合的锚定残基。在衣壳蛋白序列C(263 - 275)内鉴定出重叠的CD4 + 和CD8 + T细胞表位,这暗示了在基于肽的风疹候选疫苗中使用此类表位的策略。

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