Journal
AMERICAN JOURNAL OF TRANSPLANTATION
Volume 13, Issue 11, Pages 2842-2854Publisher
ELSEVIER SCIENCE INC
DOI: 10.1111/ajt.12431
Keywords
Acute cellular rejection; BKV; differential diagnosis; kidney transplantation; next generation sequencing; polyoma
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Funding
- EFRE (Profit) [10145620]
- BMBF (Primage)
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Clonotype analysis is essential for complete characterization of antigen-specific T cells. Moreover, knowledge on clonal identity allows tracking of antigen-specific T cells in whole blood and tissue infiltrates and can provide information on antigenic specificity. Here, we developed a next generation sequencing (NGS)-based platform for the highly quantitative clonotype characterization of T cells and determined requirements for the unbiased characterization of the input material (DNA, RNA, ex vivo derived or cell culture expanded T cells). Thereafter we performed T cell receptor (TCR) repertoire analysis of various specimens in clinical settings including cytomegalovirus (CMV), polyomavirus BK (BKV) reactivation and acute cellular allograft rejection. Our results revealed dynamic nature of virus-specific T cell clonotypes; CMV reactivation was linked to appearance of new highly abundant antigen-specific clonalities. Moreover, analysis of clonotype overlap between BKV-, alloantigen-specific T cell-, kidney allograft- and urine-derived lymphocytes provided hints for the differential diagnosis of allograft dysfunction and enabled appropriate therapy adjustment. We believe that the established approach will provide insights into the regulation of virus-specific/anti-tumor immunity and has high diagnostic potential in the clinical routine. This study describes the development and characterization of T cell receptor repertoire analysis based on Next Generation Sequencing and its application for complex differential diagnosis of posttransplant kidney dysfunction.
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