Pogorelyy Mikhail V, Elhanati Yuval, Marcou Quentin, Sycheva Anastasiia L, Komech Ekaterina A, Nazarov Vadim I, Britanova Olga V, Chudakov Dmitriy M, Mamedov Ilgar Z, Lebedev Yury B, Mora Thierry, Walczak Aleksandra M
Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Moscow, Russian Federation.
Laboratoire de physique théorique, CNRS, UPMC and École normale supérieure, Paris, France.
PLoS Comput Biol. 2017 Jul 6;13(7):e1005572. doi: 10.1371/journal.pcbi.1005572. eCollection 2017 Jul.
The diversity of T-cell receptors recognizing foreign pathogens is generated through a highly stochastic recombination process, making the independent production of the same sequence rare. Yet unrelated individuals do share receptors, which together constitute a "public" repertoire of abundant clonotypes. The TCR repertoire is initially formed prenatally, when the enzyme inserting random nucleotides is downregulated, producing a limited diversity subset. By statistically analyzing deep sequencing T-cell repertoire data from twins, unrelated individuals of various ages, and cord blood, we show that T-cell clones generated before birth persist and maintain high abundances in adult organisms for decades, slowly decaying with age. Our results suggest that large, low-diversity public clones are created during pre-natal life, and survive over long periods, providing the basis of the public repertoire.
识别外来病原体的T细胞受体的多样性是通过一个高度随机的重组过程产生的，使得相同序列的独立产生非常罕见。然而，不相关的个体确实共享受体，这些受体共同构成了一个由丰富克隆型组成的“公共”库。TCR库最初在产前形成，此时插入随机核苷酸的酶被下调，产生一个有限多样性的子集。通过对双胞胎、不同年龄的不相关个体和脐带血的深度测序T细胞库数据进行统计分析，我们发现出生前产生的T细胞克隆在成年生物体中持续存在并保持高丰度数十年，随年龄增长而缓慢衰减。我们的结果表明，大型、低多样性的公共克隆在产前形成，并长期存活，为公共库提供了基础。
