Harnessing the diversity of the human T-cell repertoire: a monitoring tool for transplantation tolerance?

There is significant diversity in the TCR repertoire in heterologous and allogeneic immunity. A paper in this issue of the European Journal of Immunology shows that changes in the TCR repertoire can be correlated with outcomes of renal transplantation. This indicates that the diversity of the TCR repertoire could be utilized to monitor clinical phenotypes, such as chronic humoral rejection and operational tolerance in organ transplantation. However, prior to the clinical use of monitoring changes in the TCR repertoire as a biomarker to monitor clinical status after organ transplantation, many questions regarding time dependency, triggering factors and specificity need to be addressed. A causative role for TCR repertoire disruption in organ transplantation will need to be proven by interventional trials that can demonstrate that the TCR repertoire is modifiable and predictive of graft outcome. In this Commentary, we discuss the strengths and opportunities of TCR repertoire monitoring, and point towards yet unanswered questions that will become important if the Vβ CDR3-length distribution assay will be clinically applied.