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在表达来自H-2b限制性、2,4,6-三硝基苯基(TNP)特异性溶细胞性T细胞克隆的T细胞受体β链基因的转基因小鼠中,H-2b限制性、TNP特异性细胞毒性T淋巴细胞前体的频率增加。

Increased frequency of 2,4,6-trinitrophenyl (TNP)-specific, H-2b-restricted cytotoxic T lymphocyte precursors in transgenic mice expressing a T cell receptor beta chain gene from an H-2b-restricted, TNP-specific cytolytic T cell clone.

作者信息

Iglesias A, Hansen-Hagge T, Von Bonin A, Weltzien H U

机构信息

Max-Planck-Institut für Immunbiologie, FRG.

出版信息

Eur J Immunol. 1992 Feb;22(2):335-41. doi: 10.1002/eji.1830220208.

Abstract

T cell antigen receptors (TcR) expressing V alpha 10/J alpha BBM142 genes in association with beta chains containing J beta 2.6 elements were found to be predominant among 2,4,6-trinitrophenyl (TNP)-specific, H-2b-restricted cytolytic T cell lines (CTL). To assess the relative contribution of the TcR beta chain to the TNP specificity as well as to the selection of the respective TcR alpha chain elements we generated transgenic mice expressing the TcR beta chain of the H-2b/TNP-specific CTL clone BT7.4.1. The TcR of this clone does not belong to the type predominant among H-2b/TNP-specific CTL, as it consists of an alpha chain encoded by a V alpha 8/J alpha DO gene rearrangement and a V beta 2/J beta 1.1-containing beta chain. In the transgenic mice almost all T cells exclusively express the transgenic V beta 2 gene, as a result of allelic exclusion. TNP-specific, H-2b-restricted precursors were found at 7- to 8-fold higher frequency in these mice as compared with non-transgenic littermates. In H-2b/d heterozygous transgenic mice, an increased frequency of TNP-specific precursors was found only in H-2b, but not in H-2d-restricted CTL. Analysis of H-2b/TNP-specific CTL lines derived from V beta 2-transgenic mice indicated a preferential association of the transgenic TcR beta chain with endogenous alpha chains encoded by V alpha 8 and J alpha BBM142 genes. This suggests that the hapten TNP is recognized like typical peptide antigens by combinatorial TcR alpha and beta contact sites.

摘要

在2,4,6-三硝基苯(TNP)特异性、H-2b限制性细胞毒性T细胞系(CTL)中,发现表达Vα10/JαBBM142基因并与含有Jβ2.6元件的β链相关联的T细胞抗原受体(TcR)占主导地位。为了评估TcRβ链对TNP特异性以及各自TcRα链元件选择的相对贡献,我们构建了表达H-2b/TNP特异性CTL克隆BT7.4.1的TcRβ链的转基因小鼠。该克隆的TcR不属于H-2b/TNP特异性CTL中占主导地位的类型,因为它由Vα8/JαDO基因重排编码的α链和含有Vβ2/Jβ1.1的β链组成。在转基因小鼠中,由于等位基因排斥,几乎所有T细胞都只表达转基因Vβ2基因。与非转基因同窝小鼠相比,在这些小鼠中发现TNP特异性、H-2b限制性前体细胞的频率高7至8倍。在H-2b/d杂合转基因小鼠中,仅在H-2b限制性CTL中发现TNP特异性前体细胞频率增加,而在H-2d限制性CTL中未发现。对源自Vβ2转基因小鼠的H-2b/TNP特异性CTL系的分析表明,转基因TcRβ链与由Vα8和JαBBM142基因编码的内源性α链优先关联。这表明半抗原TNP像典型的肽抗原一样被组合的TcRα和β接触位点识别。

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