T Cell Receptor Repertoire Analysis of BKV-Specific T Cells in Peripheral Blood Samples By Next Generation Sequencing Reveals Differential Role and Kinetics of CD4 and CD8 T Cell Clones in Viral Control
1Berlin-Brandenburg Center for Regenerative Therapies, Berlin, Germany
2Department of Computer Science, Free University, Berlin, Germany
3Max Planck Institute for Molecular Genetics, Berlin, Germany
4Charite University-Medicine, Berlin, Germany.
Meeting: 2015 American Transplant Congress
Abstract number: 430
Keywords: Kidney transplantation, Polyma virus, T cell receptors (TcR)
Session Information
Date: Tuesday, May 5, 2015
Session Name: Concurrent Session: BK Virus Infection After Kidney Transplantation
Session Time: 4:00pm-5:30pm
Presentation Time: 4:48pm-5:00pm
Location: Room 115-C
Background:
BKV-specific T cells play the crucial role in controlling virus reactivation and analyses of their frequencies have been previously performed in different studies. However, nothing is known about the clonotypic repertoire of BKV-specific T cells, kinetics of BKV-specific T cell clones in clinical course and the role of clonotypic diversity in virus control. Very recently, we established next-generation sequencing (NGS)-based T cell receptor (TCR) analysis of antigen-specific T cells allowing detailed quantitative evaluation of high and low abundance clones and single clone tracking in peripheral blood and tissues.
Methods and Results:
We applied the established TCR-NGS-methodology for the analysis of BKV-specific clones in kidney transplant recipients during the clinical course of BKV reactivation. Enriched BKV-specific and whole blood derived CD4 and CD8 T cells were analyzed in parallel to viral load measurements. Analysis of enriched BKV-specific T cells showed reverse correlation of clonotype diversity and viral load (Pearson -0.745). Further, based on TCR-assigned identity single BKV-specific T cells were tracked in peripheral blood at different time points. We showed here differential behavior of BKV-specific CD8 and CD4 clones. While minimal kinetics occurred in CD8 clones, significant changes of CD4 clones were observed. In addition, the vast majority of high and low abundance CD4 clones were present in peripheral blood but showed differential behavior. One clonal group increased during viral reactivation and consequent clearance. The other group remained stable. This repertoire behavior suggests the functional importance of certain BKV-specific clones in terms of virus control.
Conclusions:
We showed here the importance of diverse CD4 clonotypes for control of BKV reactivation after kidney transplantation. Further, we showed differential dynamics of single BKV-specific CD8 and CD4 clones and their connection to virus control. The knowledge on clonotype diversity and tracking of certain single clones would allow prediction of viral reactivation and successful sample selection for adoptive cell transfer therapies.
To cite this abstract in AMA style:
Nienen M, Benjamin W, Kuchenbecker L, Hecht J, Reinke P, Neumann A, Babel N. T Cell Receptor Repertoire Analysis of BKV-Specific T Cells in Peripheral Blood Samples By Next Generation Sequencing Reveals Differential Role and Kinetics of CD4 and CD8 T Cell Clones in Viral Control [abstract]. Am J Transplant. 2015; 15 (suppl 3). https://atcmeetingabstracts.com/abstract/t-cell-receptor-repertoire-analysis-of-bkv-specific-t-cells-in-peripheral-blood-samples-by-next-generation-sequencing-reveals-differential-role-and-kinetics-of-cd4-and-cd8-t-cell-clones-in-viral-contr/. Accessed July 8, 2020.« Back to 2015 American Transplant Congress