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CDR3 and V genes show distinct reconstitution patterns in T cell repertoire post-allogeneic bone marrow transplantation
Immunogenetics ( IF 2.9 ) Pub Date : 2021-01-21 , DOI: 10.1007/s00251-020-01200-7
Nili Tickotsky-Moskovitz 1 , Yoram Louzoun 2 , Shirit Dvorkin 2 , Adi Rotkopf 3 , Amir Asher Kuperman 3, 4 , Sol Efroni 1
Affiliation  

Restoration of T cell repertoire diversity after allogeneic bone marrow transplantation (allo-BMT) is crucial for immune recovery. T cell diversity is produced by rearrangements of germline gene segments (V (D) and J) of the T cell receptor (TCR) α and β chains, and selection induced by binding of TCRs to MHC-peptide complexes. Multiple measures were proposed for this diversity. We here focus on the V-gene usage and the CDR3 sequences of the beta chain. We compared multiple T cell repertoires to follow T cell repertoire changes post-allo-BMT in HLA-matched related donor and recipient pairs. Our analyses of the differences between donor and recipient complementarity determining region 3 (CDR3) beta composition and V-gene profile show that the CDR3 sequence composition does not change during restoration, implying its dependence on the HLA typing. In contrast, V-gene usage followed a time-dependent pattern, initially following the donor profile and then shifting back to the recipients' profile. The final long-term repertoire was more similar to that of the recipient's original one than the donor’s; some recipients converged within months, while others took multiple years. Based on the results of our analyses, we propose that donor-recipient V-gene distribution differences may serve as clinical biomarkers for monitoring immune recovery.



中文翻译:

CDR3 和 V 基因在异基因骨髓移植后的 T 细胞库中显示出不同的重建模式

同种异体骨髓移植 (allo-BMT) 后 T 细胞库多样性的恢复对于免疫恢复至关重要。T 细胞多样性是由 T 细胞受体 (TCR) α 和 β 链的种系基因片段(V(D)和 J)重排以及 TCR 与 MHC-肽复合物结合诱导的选择产生的。针对这种多样性提出了多种措施。我们在这里关注 V 基因的使用和 β 链的 CDR3 序列。我们比较了多个 T 细胞库,以跟踪 HLA 匹配的相关供体和受体对中异体 BMT 后 T 细胞库的变化。我们对供体和受体互补决定区 3 (CDR3) β 组成和 V 基因谱之间差异的分析表明,CDR3 序列组成在恢复过程中不会改变,这意味着它依赖于 HLA 分型。相比之下,V 基因的使用遵循时间依赖性模式,最初遵循捐赠者的个人资料,然后又转回接受者的个人资料。最终的长期曲目与接受者的原始曲目比捐赠者的更相似;一些接受者在几个月内就收敛了,而另一些则需要数年时间。根据我们的分析结果,我们建议供体-受体 V 基因分布差异可以作为监测免疫恢复的临床生物标志物。

更新日期:2021-01-21
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