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

Babel, Nina MD1,2,3; Stervbo, Ulrik PhD2; Reinke, Petra MD1,4; Volk, Hans-Dieter MD1,3,4

doi: 10.1097/TP.0000000000002776
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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.

1 Berlin-Brandenburg Center for Regenerative Therapies (BCRT), Charité-Universitätsmedizin Berlin, Augustenburger Platz 1, Berlin, Germany.

2 Medical Department I, Universitätsklinikum der Ruhr-Universität Bochum, Ruhr-Universität Bochum, Hölkeskampring 40, Herne, Germany.

3 Institute for Medical Immunology, Charité-Universitätsmedizin Berlin, Augustenburger Platz 1, Berlin, Germany.

4 Berlin Center for Advanced Therapies (BECAT), Charité-Universitätsmedizin Berlin, Augustenburger Platz 1, Berlin, Germany.

Received 14 November 2018. Revision received 15 March 2019.

Accepted 1 April 2019.

BMBF grant e:KID to N.B. and P.R.; BCRT to N.B., P.R., H.D.V.; EFRE grant OsteoSys to N.B.; EC horizon 2020 program “Reshape” consortium P.R. and H.D.V. The other authors declare no conflict of interest.

N.B. designed concept and figures and wrote the article. U.S. contributed to writing, revised the article, designed, and drew figures. P.R. delivered information to own data and revised the article. H.-D.V. contributed to writing, revised, and edited the article.

Correspondence: Nina Babel, Berlin-Brandenburg Center for Regenerative Therapies (BCRT), Charité-Universitätsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany. (nina.babel@charite.de).

Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.