Analysis of T-Cell Receptor Repertoire in Transplantation: Fingerprint of T Cell-mediated Alloresponse.

Guangyao Tian,Guoyue Lv,Mingqian Li

doi:10.3389/fimmu.2021.778559

Guangyao Tian, Guoyue Lv + Show 1 more

Open Access

https://doi.org/10.3389/fimmu.2021.778559

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Abstract

T cells play a key role in determining allograft function by mediating allogeneic immune responses to cause rejection, and recent work pointed their role in mediating tolerance in transplantation. The unique T-cell receptor (TCR) expressed on the surface of each T cell determines the antigen specificity of the cell and can be the specific fingerprint for identifying and monitoring. Next-generation sequencing (NGS) techniques provide powerful tools for deep and high-throughput TCR profiling, and facilitate to depict the entire T cell repertoire profile and trace antigen-specific T cells in circulation and local tissues. Tailing T cell transcriptomes and TCR sequences at the single cell level provides a full landscape of alloreactive T-cell clones development and biofunction in alloresponse. Here, we review the recent advances in TCR sequencing techniques and computational tools, as well as the recent discovery in overall TCR profile and antigen-specific T cells tracking in transplantation. We further discuss the challenges and potential of using TCR sequencing-based assays to profile alloreactive TCR repertoire as the fingerprint for immune monitoring and prediction of rejection and tolerance.

Highlights

T cells recognize antigens through their T-cell receptor (TCR) binding to antigen-presenting cells (APCs) surface peptidemajor histocompatibility complex [1]
Linking the TCR repertoire with gene expression profiles led to further information, enabling to trace of specific T cells developmental fate and biofunction
In the setting of transplantation, the dynamics of the overall TCR repertoires after transplantation are closely related to the immune status after transplantation

Summary

INTRODUCTION

T cells recognize antigens through their TCRs binding to antigen-presenting cells (APCs) surface peptidemajor histocompatibility complex (pMHC) [1]. This distinct distribution of T cell pool between liver-graft and blood was demonstrated by Mederacke et al They used a time-saving MLR method by incubating recipient T cells sample for 24 hours with irradiated donor splenocytes as stimulators prior to transplantation, and subsequently sorted and sequenced the CD154 positive cell as alloreactive effector T cells (Teffs) [105] to construct the HVG TCR library [135, 136] (Figure 3C) They tracked HVG reactive T-cell clones at multiple time points in blood samples, and reidentified those clones in the liver biopsies. The cells driving alloresponse may be small in number, and the alloreactive TCR repertoires in each small cohort may be drowned out in TABLE 2 | Summary of methods for linking TCR-antigen specificity

Method

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CONCLUSIONS