CDR3 and V genes show distinct reconstitution patterns in T cell repertoire post-allogeneic bone marrow transplantation

Immunogenetics. 2021 Apr;73(2):163-173. doi: 10.1007/s00251-020-01200-7. Epub 2021 Jan 21.

Abstract

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.

Keywords: Bone marrow; Immunology; Repertoire; T cell; Transplantation.

MeSH terms

  • Adult
  • Bone Marrow Transplantation*
  • Complementarity Determining Regions / genetics*
  • Female
  • Gene Rearrangement, beta-Chain T-Cell Antigen Receptor
  • Genes, T-Cell Receptor beta / genetics*
  • Histocompatibility Testing
  • Humans
  • Male
  • Middle Aged
  • Receptors, Antigen, T-Cell, alpha-beta / genetics
  • T-Lymphocytes / immunology*
  • Tissue Donors
  • Transplantation, Homologous

Substances

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