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

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

Abstract

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.

Keywords: Allogeneic hematopoietic stem cell transplantation; Complementarity-determining region 3; Cytomegalovirus; High-throughput sequencing; T cell receptor.

MeSH terms

  • Adolescent
  • Adult
  • Complementarity Determining Regions / genetics
  • Computational Biology / methods
  • Cytomegalovirus Infections* / immunology
  • Cytomegalovirus Infections* / virology
  • Cytomegalovirus* / genetics
  • Cytomegalovirus* / immunology
  • Female
  • Genotype
  • Hematopoietic Stem Cell Transplantation* / adverse effects
  • High-Throughput Nucleotide Sequencing
  • Humans
  • Male
  • Middle Aged
  • Receptors, Antigen, T-Cell* / genetics
  • Receptors, Antigen, T-Cell* / immunology
  • T-Lymphocytes / immunology
  • Transplant Recipients
  • Transplantation, Homologous* / adverse effects
  • Virus Activation
  • Young Adult

Substances

  • Receptors, Antigen, T-Cell
  • Complementarity Determining Regions