Clinical and basic implications of dynamic T cell receptor clonotyping in hematopoietic cell transplantation.

Clinical and basic implications of dynamic T cell receptor clonotyping in hematopoietic cell transplantation.
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DOI:
10.1172/jci.insight.149080
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发表时间:
2021-07-08
期刊:
影响因子:
8
通讯作者:
Maciejewski JP
Maciejewski JP
中科院分区:
医学1区
文献类型:
--
作者:
Pagliuca S;Gurnari C;Hong S;Zhao R;Kongkiatkamon S;Terkawi L;Zawit M;Guan Y;Awada H;Kishtagari A;Kerr CM;LaFramboise T;Patel BJ;Jha BK;Carraway HE;Visconte V;Majhail NS;Hamilton BK;Maciejewski JP

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TCR库多样化构成了异基因造血细胞移植(allo-HCT)后成功免疫重建的基础。对来自35名allo-HCT受者/供者队列的135份系列标本进行了深度TCR Vβ测序,以分析移植后TCR结构和动力学。配对分析的克隆型剧目显示与供体扩增的重叠最小。稀疏和过度扩增的克隆型模式是T细胞重建的标志,并影响临床结果。供体和移植前TCR多样性以及I类人类白细胞抗原基因型的差异是受体TCR库恢复的主要预测因素。互补决定区3为基础的特异性谱分析表明,在后期allo-HCT阶段的病原体和肿瘤相关的克隆型的主要扩展,而自身反应性克隆的情况下,移植物抗宿主病的发生更扩大。这些发现揭示了allo-HCT后的适应性免疫重建过程,并可能有助于追踪同种异体反应性反应。
TCR repertoire diversification constitutes a foundation for successful immune reconstitution after allogeneic hematopoietic cell transplantation (allo-HCT). Deep TCR Vβ sequencing of 135 serial specimens from a cohort of 35 allo-HCT recipients/donors was performed to dissect posttransplant TCR architecture and dynamics. Paired analysis of clonotypic repertoires showed a minimal overlap with donor expansions. Rarefied and hyperexpanded clonotypic patterns were hallmarks of T cell reconstitution and influenced clinical outcomes. Donor and pretransplant TCR diversity as well as divergence of class I human leukocyte antigen genotypes were major predictors of recipient TCR repertoire recovery. Complementary determining region 3–based specificity spectrum analysis indicated a predominant expansion of pathogen- and tumor-associated clonotypes in the late post–allo-HCT phase, while autoreactive clones were more expanded in the case of graft-versus-host disease occurrence. These findings shed light on post–allo-HCT adaptive immune reconstitution processes and possibly help in tracking alloreactive responses.
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