异基因造血干细胞移植后受者巨细胞病毒相关 T 细胞受体的研究进展。

Insights into cytomegalovirus-associated T cell receptors in recipients following allogeneic hematopoietic stem cell transplantation.

机构信息

Department of Clinical Laboratory, Department of "A", Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou, 310053, China.

The Third Affiliated Hospital of Zhejiang, Chinese Medical University, Zhongshan Hospital of Zhejiang Province, Hangzhou, China.

出版信息

Virol J. 2024 Sep 30;21(1):236. doi: 10.1186/s12985-024-02511-x.

BACKGROUND

Cytomegalovirus (CMV) reactivation is a serious problem in recipients of allogeneic hematopoietic stem cell transplantation. Long-term latency depends on specific T cell immune reconstitution, which identifies various pathogens by T cell receptors (TCRs). However, the mechanisms underlying the selection of CMV-specific TCRs in recipients after transplantation remain unclear.

METHODS

Using high-throughput sequencing and bioinformatics analysis, the T cell immune repertoire of seven CMV reactivated recipients (CRRs) were analyzed and compared to those of seven CMV non-activated recipients (CNRs) at an early stage after transplant.

RESULTS

The counts of unique complementarity-determining region 3 (CDR3) were significantly higher in CNRs than in CRRs. The CDR3 clones in the CNRs exhibit higher homogeneity compared to the CRRs. With regard to T cell receptor β-chain variable region (TRBV) and joint region (TRBJ) genotypes, significant differences were observed in the frequencies of TRBV6, BV23, and BV7-8 between the two groups. In addition to TRBV29-1/BJ1-2, TRBV2/BJ2-2, and TRBV12-4/BJ1-5, 11 V-J combinations had significantly different expression levels between CRRs and CNRs.

CONCLUSIONS

The differences in TCR diversity, TRBV segments, and TRBV-BJ combinations observed between CNRs and CRRs might be associated with post-transplant CMV reactivation and could serve as a foundation for further research.

背景

巨细胞病毒（CMV）再激活是异基因造血干细胞移植受者的一个严重问题。长期潜伏依赖于特定的 T 细胞免疫重建，T 细胞受体（TCRs）通过 T 细胞识别各种病原体。然而，移植后受者中 CMV 特异性 TCR 选择的机制仍不清楚。

方法

使用高通量测序和生物信息学分析，在移植后早期分析了 7 例 CMV 再激活受者（CRR）和 7 例 CMV 非激活受者（CNR）的 T 细胞免疫受体库，并进行了比较。

结果

CNR 中独特互补决定区 3（CDR3）的计数明显高于 CRR。与 CRR 相比，CNR 中的 CDR3 克隆表现出更高的同质性。在 T 细胞受体β链可变区（TRBV）和连接区（TRBJ）基因型方面，两组之间 TRBV6、BV23 和 BV7-8 的频率存在显著差异。除了 TRBV29-1/BJ1-2、TRBV2/BJ2-2 和 TRBV12-4/BJ1-5 之外，11 个 V-J 组合在 CRR 和 CNR 之间的表达水平也有显著差异。