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胎儿胸腺与成人胸腺之间不同的T细胞受体（TCR）基因片段使用情况及MHC限制。

Distinct T-cell receptor (TCR) gene segment usage and MHC-restriction between foetal and adult thymus.

作者信息

Rowell Jasmine, Lau Ching-In, Ross Susan, Yanez Diana C, Peña Oscar A, Chain Benny, Crompton Tessa

机构信息

UCL Great Ormond Street Institute of Child Health, London, United Kingdom.

School of Biochemistry, University of Bristol, Bristol, United Kingdom.

出版信息

Elife. 2024 Dec 5;13:RP93493. doi: 10.7554/eLife.93493.

DOI:10.7554/eLife.93493
PMID:39636212
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11620746/
Abstract

Here, we sequenced rearranged TCRβ and TCRα chain sequences in CD4CD8 double positive (DP), CD4CD8 single positive (SP4) and CD4CD8 (SP8) thymocyte populations from the foetus and young adult mouse. We found that life-stage had a greater impact on TCRβ and TCRα gene segment usage than cell-type. Foetal repertoires showed bias towards 3'TRAV and 5'TRAJ rearrangements in all populations, whereas adult repertoires used more 5'TRAV gene segments, suggesting that progressive TCRα rearrangements occur less frequently in foetal DP cells. When we synchronised young adult DP thymocyte differentiation by hydrocortisone treatment the new recovering DP thymocyte population showed more foetal-like 3'TRAV and 5'TRAJ gene segment usage. In foetus we identified less influence of MHC-restriction on α-chain and β-chain combinatorial VxJ usage and CDR1xCDR2 (V region) usage in SP compared to adult, indicating weaker impact of MHC-restriction on the foetal TCR repertoire. The foetal TCRβ repertoire was less diverse, less evenly distributed, with fewer non-template insertions, and all foetal populations contained more clonotypic expansions than adult. The differences between the foetal and adult thymus TCR repertoires are consistent with the foetal thymus producing αβT-cells with properties and functions that are distinct from adult T-cells: their repertoire is less governed by MHC-restriction, with preference for particular gene segment usage, less diverse with more clonotypic expansions, and more closely encoded by genomic sequence.

摘要

在此，我们对来自胎儿和成年小鼠的CD4CD8双阳性（DP）、CD4CD8单阳性（SP4）和CD4CD8（SP8）胸腺细胞群体中的重排TCRβ和TCRα链序列进行了测序。我们发现，生命阶段对TCRβ和TCRα基因片段使用的影响比细胞类型更大。胎儿的TCR库在所有群体中都表现出对3'TRAV和5'TRAJ重排的偏向，而成体的TCR库使用更多的5'TRAV基因片段，这表明胎儿DP细胞中渐进性TCRα重排的发生频率较低。当我们通过氢化可的松处理同步成年DP胸腺细胞分化时，新恢复的DP胸腺细胞群体表现出更多类似胎儿的3'TRAV和5'TRAJ基因片段使用情况。在胎儿中，我们发现与成年相比，MHC限制对α链和β链组合VxJ使用以及SP中CDR1xCDR2（V区）使用的影响较小，表明MHC限制对胎儿TCR库的影响较弱。胎儿的TCRβ库多样性较低、分布不均匀、非模板插入较少，并且所有胎儿群体中的克隆型扩增都比成年群体更多。胎儿和成年胸腺TCR库之间的差异与胎儿胸腺产生具有不同于成年T细胞的特性和功能的αβT细胞一致：它们的库受MHC限制的影响较小，偏好特定基因片段的使用，多样性较低但克隆型扩增更多，并且由基因组序列编码得更紧密。

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3
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