The Identity Card of T Cells-Clinical Utility of T-cell Receptor Repertoire Analysis in Transplantation

Abstract

There is a clear medical need to change the current strategy of "one-size-fits-all" immunosuppression for controlling transplant rejection to precision medicine and targeted immune intervention. As T cells play a key role in both undesired graft rejection and protection, a better understanding of the fate and function of both alloreactive graft-deteriorating T cells and those protecting to infections is required. The T-cell receptor (TCR) is the individual identity card of each T cell clone and can help to follow single specificities. In this context, tracking of lymphocytes with certain specificity in blood and tissue in clinical follow up is of especial importance. After overcoming technical limitations of the past, novel molecular technologies opened new avenues of diagnostics. Using advantages of next generation sequencing, a method was established for T-cell tracing by detection of variable TCR region as identifiers of individual lymphocyte clones. The current review describes principles of laboratory and computational methods of TCR repertoire analysis, and gives an overview on applications for the basic understanding of transplant biology and immune monitoring. The review also delineates methodological pitfalls and challenges. With the outlook on prediction of antigens in immune-mediated processes including those of unknown causative pathogens, monitoring the fate and function of individual T cell clones, and the adoptive transfer of protective effector or regulatory T cells, this review highlights the current and future capability of TCR repertoire analysis.