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T-cell receptor retrogenic mice: A rapid, flexible alternative to T-cell receptor transgenic mice

机译:T细胞受体逆转小鼠:快速,灵活的替代T细胞受体转基因小鼠

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摘要

The T-cell receptor (TCR) is unique in its complexity. It determines not only positive (life) and negative (death) selection in the thymus, but also mediates proliferation, anergy, differentiation, cytotoxicity and cytokine production in the periphery. Through its association with six CD3 signalling chains (εγ, δε and ζζ), the TCR is capable of recognizing an extensive variety of antigenic peptides, from both pathogens and self-antigens, and translating these interactions into multiple signalling pathways that mediate diverse T-cell developmental and functional responses. The analysis of TCR biology has been revolutionized by the development of TCR transgenic mice, which express a single clonotypic T-cell population, with diverse specificities and genetic backgrounds. However, they are time consuming to generate and characterize, limiting the analysis of large numbers of TCR over a short period of time in multiple genetic backgrounds. The recent development of TCR retrogenic technology resolves these limitations and could in time have a similarly important impact on our understanding of T-cell development and function. In this review, we will discuss the advantages and limitations of retrogenic technology compared with the generation and use of TCR transgenic mice for studying all aspects of T-cell biology.
机译:T细胞受体(TCR)具有独特的复杂性。它不仅决定了胸腺中阳性(生命)和阴性(死亡)的选择,而且还介导了外周增殖,无反应,分化,细胞毒性和细胞因子的产生。通过与六个CD3信号链(εγ,δε和ζζ)结合,TCR能够识别来自病原体和自身抗原的多种抗原肽,并将这些相互作用转化为介导多种T-细胞发育和功能反应。 TCR转基因小鼠的开发已经彻底改变了TCR生物学的分析方法,该小鼠表达具有多种特异性和遗传背景的单个克隆型T细胞群体。但是,它们的生成和表征非常耗时,从而限制了在多个遗传背景下短时间内对大量TCR的分析。 TCR逆转录技术的最新发展解决了这些限制,并且可能及时对我们对T细胞发育和功能的理解产生类似的重要影响。在这篇综述中,我们将讨论与TCR转基因小鼠的产生和使用相比,逆转录技术在研究T细胞生物学各个方面的优势和局限性。

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