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Assessing T Cell Clonal Size Distribution: A Non-Parametric Approach

机译:评估T细胞克隆大小分布:一种非参数方法

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摘要

Clonal structure of the human peripheral T-cell repertoire is shaped by a number of homeostatic mechanisms, including antigen presentation, cytokine and cell regulation. Its accurate tuning leads to a remarkable ability to combat pathogens in all their variety, while systemic failures may lead to severe consequences like autoimmune diseases. Here we develop and make use of a non-parametric statistical approach to assess T cell clonal size distributions from recent next generation sequencing data. For 41 healthy individuals and a patient with ankylosing spondylitis, who undergone treatment, we invariably find power law scaling over several decades and for the first time calculate quantitatively meaningful values of decay exponent. It has proved to be much the same among healthy donors, significantly different for an autoimmune patient before the therapy, and converging towards a typical value afterwards. We discuss implications of the findings for theoretical understanding and mathematical modeling of adaptive immunity.
机译:人外周T细胞库的克隆结构受多种稳态机制影响,包括抗原呈递,细胞因子和细胞调节。它的精确调整可导致出色的抵抗各种病原体的能力,而系统性衰竭可能会导致严重后果,例如自身免疫性疾病。在这里,我们开发并利用一种非参数统计方法从最近的下一代测序数据中评估T细胞克隆大小分布。对于接受治疗的41名健康个体和强直性脊柱炎患者,我们总是发现幂律在几十年内呈比例变化,并首次计算了衰减指数的定量有意义的值。在健康的捐献者中,这一点已被证明是完全相同的,对于治疗前的自身免疫患者而言,其差异是很大的,之后便趋于典型值。我们讨论了发现的含义对适应性免疫的理论理解和数学建模。

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