A fractal clonotype distribution in the CD8+ memory T cell repertoire could optimize potential for immune responses
A fractal clonotype distribution in the CD8+ memory T cell repertoire could optimize potential for immune responses
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DOI：
10.4049/jimmunol.170.8.3994
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发表时间：
2003-04-15
影响因子：
4.4
通讯作者：
Gorski, J
中科院分区：
文献类型：
--
作者：
Naumov, YN;Naumova, EN;Gorski, J
CD8(+)T细胞记忆的本质仍不完全清楚。我们以前已经报道过，对人类白细胞抗原42限制性流感衍生肽的反应会导致复杂的T细胞谱系。在这项研究中，我们扩展了这一分析，并更严格地描述了曲目。在一个个体中，我们根据TCRβ链第三互补决定区域的独特DNA序列定义了141个不同的T细胞克隆型。克隆型的频率分布；不是预期的正态分布，而是以大的低频尾巴为特征。复杂群体的存在表明了在内存池中以低频率维持大量Ag特异性克隆型的机制。通过对克隆类型进行排序，我们可以用类似于1.6的衰减率参数来描述种群的指数分布。如果将谱系分成几个子集，例如使用BJ2.7的克隆型，或者其第三互补决定区编码氨基酸序列IRSS的克隆型，克隆型频率也可以用类似于幂函数的分布来描述。这表明了与曲目的自我相似性，在曲目中，较小的曲目是较大曲目的略微改变的副本。这种类似于幂定律的描述随着时间的推移是稳定的，并在第二个个体中观察到了这种描述。可以使用递归算法将克隆类型在曲库中的分布映射到多边形螺旋上。自相似、幂定律和递归映射算法与分形系统相关。因此，抗原特异性记忆CD8 T细胞谱系可以被认为是分形的，这可能表明优化的灵活性和稳健性。
The nature of CD8(+) T cell memory is still incompletely understood. We have previously reported that the response to an HLA-42-restricted influenza-derived peptide results in a complex T cell repertoire. In this study we extend this analysis and describe the repertoire with more rigor. In one individual we defined 141 distinct T cell clonotypes on the basis of the unique DNA sequence of the third complementarity-determining region of the TCR beta-chain. The frequency distribution of the clonotypes; is not what is expected of a normal distribution but is characterized by a large low-frequency tail. The existence of a complex population indicates a mechanism for maintaining a large number of Ag-specific clonotypes at a low frequency in the memory pool. Ranking the clonotypes allowed us to describe the population in terms of a power law-like distribution with a parameter of decay of similar to1.6. If the repertoire is divided into subsets, such as clonotypes that use BJ2.7 or those whose third complementarity-determining region encodes the amino acid sequence IRSS, the clonotype frequencies could also be described by a power law-like distribution. This indicates a self similarity to the repertoire in which smaller pieces are slightly altered copies of the larger piece. The power law-like description is stable with time and was observed in a second individual. The distribution of clonotypes in the repertoire could be mapped onto a polygonal spiral using a recursive algorithm. Self similarity, power laws, and recursive mapping algorithms are associated with fractal systems. Thus, Ag-specific memory CD8 T cell repertoires can be considered as fractal, which could indicate optimized flexibility and robustness.