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1-丙基-1-亚硝基脲诱导的胸腺淋巴瘤中TCR-β、TCR-γ、CD4和CD8的偏离性过表达:TCR-β等位基因排斥的破坏以及功能性TCR-βγ异二聚体在淋巴瘤cFTL53上的表达

Deviated overexpression of TCR-beta, TCR-gamma, CD4, and CD8 on thymic lymphomas induced by 1-propyl-1-nitrosourea: destruction of the allelic exclusion of TCR-beta and expression of functional TCR-betagamma heterodimer on a lymphoma, cFTL53.

作者信息

Kinebuchi M, Matsuura A, Ogiu T, Kikuchi K

机构信息

Department of Pathology, School of Medicine, Sapporo Medical University, Chuo-ku, Japan.

出版信息

J Immunol. 1997 Jul 15;159(2):748-56.

PMID:9218591
Abstract

Thymic lymphomas (FTLs) induced by the chemical carcinogen 1-propyl-1-nitrosourea (PNU) in F344 rats showed deviated overexpression of TCR-beta, TCR-gamma, CD4, and CD8. Even though most FTLs were in the CD4+ CD8+ stage, all FTLs expressed TCR-beta mRNA with TCR-gamma mRNA, but without TCR-alpha mRNA or TCR-delta mRNA. One of the FTLs, cFTL53, expressed two kinds of TCR-beta mRNA and two kinds of TCR-gamma mRNA, but did not express any mRNA of TCR-alpha or TCR-delta. Both alleles of TCR-beta loci were rearranged on cFTL53. cDNA cloning and sequencing analysis showed that one TCR-gamma mRNA, Vgamma4-Jgamma1-Cgamma1, and both TCR-beta mRNA, Vbeta2-Dbeta2-Jbeta2.1 and Vbeta19-Dbeta2-Jbeta2.1-Cbeta2, on cFTL53 were in the productive form, while the other TCR-gamma mRNA, Vgamma1-Jgamma4-Cgamma4L, was not. Both TCR beta-chains and a TCR gamma-chain were expressed on cFTL53, making a novel set of TCR-betagamma heterodimer. Cross-linking of TCR-betagamma heterodimer on cFTL53 resulted in a calcium flux, indicating that TCR-betagamma works as a signal transduction receptor. Thus, there are four strange phenomena on FTLs; CD4 and CD8 are expressed without TCR-alphabeta or TCR-gammadelta, TCR-beta mRNA and TCR-gamma mRNA were expressed simultaneously without TCR-alpha and TCR-delta mRNA on FTLs, the allelic exclusion of TCR-beta was destroyed in cFTL53, and a novel set of functional TCR-betagamma heterodimer was expressed on cFTL53.

摘要

化学致癌物1-丙基-1-亚硝基脲(PNU)诱导F344大鼠产生的胸腺淋巴瘤(FTLs)表现出TCR-β、TCR-γ、CD4和CD8的异常过表达。尽管大多数FTLs处于CD4+CD8+阶段,但所有FTLs均表达TCR-β mRNA和TCR-γ mRNA,而不表达TCR-α mRNA或TCR-δ mRNA。其中一个FTL,即cFTL53,表达两种TCR-β mRNA和两种TCR-γ mRNA,但不表达TCR-α或TCR-δ的任何mRNA。TCR-β基因座的两个等位基因在cFTL53上均发生了重排。cDNA克隆和测序分析表明,cFTL53上的一种TCR-γ mRNA(Vγ4-Jγ1-Cγ1)以及两种TCR-β mRNA(Vβ2-Dβ2-Jβ2.1和Vβ19-Dβ2-Jβ2.1-Cβ2)呈有效形式,而另一种TCR-γ mRNA(Vγ1-Jγ4-Cγ4L)则不是。cFTL53上表达了两条TCR β链和一条TCR γ链,形成了一组新的TCR-βγ异二聚体。cFTL53上TCR-βγ异二聚体的交联导致钙流,表明TCR-βγ作为信号转导受体发挥作用。因此,FTLs存在四个奇怪的现象:CD4和CD8在没有TCR-αβ或TCR-γδ的情况下表达,FTLs上TCR-β mRNA和TCR-γ mRNA同时表达而没有TCR-α和TCR-δ mRNA,cFTL53中TCR-β的等位基因排斥被破坏,并且cFTL53上表达了一组新的功能性TCR-βγ异二聚体。

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