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

Abstract

AbstractBackgroundRestoration 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. This diversity can be measured by many measures. 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.ResultsOur analyses of the differences between donor and recipient complementarity determining region 3 (CDR3) beta composition and V-gene profile show that the CDR sequence composition does not change during restoration, implying its dependence on the HLA typing. In contrast, V gene usage followed a time-dependent pattern, got following the donor profile post transplant 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.ConclusionBased on the results of our analyses, we propose that donor-recipient V-gene distribution differences may serve as clinical biomarkers for monitoring immune recovery.