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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Convergent recombination shapes the clonotypic landscape of the naieve T-cell repertoire
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Convergent recombination shapes the clonotypic landscape of the naieve T-cell repertoire

机译：会聚重组塑造了幼稚T细胞库的克隆型景观

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摘要

Adaptive T-cell immunity relies on the recruitment of antigen-specific clonotypes, each defined by the expression of a distinct T-cell receptor (TCR), from an array of naive T-cell precursors. Despite the enormous clonotypic diversity that resides within the naive T-cell pool, interindividual sharing of TCR sequences has been observed within mobilized T-cell responses specific for certain peptide-major histocompatibility complex (pMHC) antigens. The mechanisms that underlie this phenomenon have not been fully elucidated, however. A mechanism of convergent recombination has been proposed to account for the occurrence of shared, or "public," TCRs in specific memory T-cell populations. According to this model, TCR sharing between individuals is directly related to TCR production frequency; this, in turn, is determined on a probabilistic basis by the relative generation efficiency of particular nucleotide and amino acid sequences during the recombination process. Here, we tested the key predictions of convergent recombination in a comprehensive evaluation of the naieve CD8~+ TCRp repertoire in mice. Within defined segments of the naieve CD8~+ T-cell repertoire, TCRβ sequences with convergent features were (i) present at higher copy numbers within individual mice and (ii) shared between individual mice. Thus, the naieve CD8~+ T-cell repertoire is not flat, but comprises a hierarchy of recurrence rates for individual clonotypes that is determined by relative production frequencies. These findings provide a framework for understanding the early mobilization of public CD8~+ T-cell clonotypes, which can exert profound biological effects during acute infectious processes.
机译：适应性T细胞免疫依赖于抗原特异性克隆型的募集，每种抗原型均由一系列原始T细胞前体的独特T细胞受体（TCR）的表达来定义。尽管原始T细胞库中存在巨大的克隆型多样性，但已在特定于某些肽-主要组织相容性复合物（pMHC）抗原的动员T细胞反应中观察到TCR序列的个体共享。但是，尚未完全阐明造成这种现象的机制。已经提出了一种融合重组的机制来解决在特定记忆T细胞群体中共享的或“公共的” TCR的出现。根据该模型，个人之间的TCR共享与TCR生产频率直接相关。反过来，这是由概率决定的，具体取决于重组过程中特定核苷酸和氨基酸序列的相对产生效率。在本文中，我们在对幼稚的CD8〜+ TCRp组成成分的综合评价中测试了聚合重组的关键预测。在幼稚的CD8〜+ T细胞库的限定片段中，具有收敛特征的TCRβ序列（i）以更高的拷贝数存在于个别小鼠中，和（ii）在个别小鼠之间共享。因此，幼稚的CD8 + T细胞库不是平坦的，而是包括由相对生产频率决定的各个克隆型的复发率层次。这些发现为了解早期动员公共CD8〜+ T细胞克隆型提供了一个框架，该模型可在急性感染过程中发挥深远的生物学作用。

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    Maire F. Quigley; Hui Yee Greenaway; Vanessa Venturi; Ross Lindsay; Kylie M. Quinn; Robert A. Seder; Daniel C. Douek; Miles P. Davenport; David A. Price;

  • 作者单位

    Human Immunology Section, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892;

    Computational Biology Unit, Centre for Vascular Research, University of New South Wales, Kensington, New South Wales 2052, Australia;

    Computational Biology Unit, Centre for Vascular Research, University of New South Wales, Kensington, New South Wales 2052, Australia;

    Cellular Immunology Laboratory, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892;

    Cellular Immunology Laboratory, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892;

    Cellular Immunology Laboratory, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892;

    Human Immunology Section, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892;

    Complex Systems in Biology Group, Centre for Vascular Research, University of New South Wales, Kensington, New South Wales 2052, Australia;

    Human Immunology Section, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892,Department of Infection, Immunity and Biochemistry, Cardiff University School of Medicine, Cardiff CF14 4XN, Wales, United Kingdom;

  • 收录信息 美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
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