A New Window into the Human Alloresponse

Transplantation. 2016 Aug;100(8):1639-49. doi: 10.1097/TP.0000000000001064.

Abstract

Alloreactive T lymphocytes are the primary mediators of allograft rejection. The size and diversity of the HLA-alloreactive T cell repertoire has thus far precluded the ability to follow these T cells and thereby to understand their fate in human transplant recipients. This review summarizes the history, challenges, and recent advances in the study of alloreactive T cells. We highlight the historical development of assays to measure alloreactivity and discuss how high-throughput T cell receptor (TCR) sequencing-based assays can provide a new window into the fate of alloreactive T cells in human transplant recipients. A specific approach combining a classical in vitro assay, the mixed lymphocyte reaction, with deep T cell receptor sequencing is described as a tool to track the donor-reactive T cell repertoire for any specific HLA-mismatched donor-recipient pair. This assay can provide mechanistic insights and has potential as a noninvasive, highly specific biomarker for rejection and tolerance.

Publication types

  • Review

MeSH terms

  • Allografts
  • Animals
  • Graft Rejection / blood
  • Graft Rejection / diagnosis*
  • Graft Rejection / immunology
  • Graft Survival
  • HLA Antigens / blood
  • HLA Antigens / immunology*
  • High-Throughput Nucleotide Sequencing*
  • Histocompatibility
  • Histocompatibility Testing / methods*
  • Humans
  • Isoantigens / blood
  • Isoantigens / immunology*
  • Lymphocyte Activation
  • Lymphocyte Culture Test, Mixed
  • Organ Transplantation / adverse effects*
  • Phenotype
  • Predictive Value of Tests
  • Receptors, Antigen, T-Cell / genetics*
  • Receptors, Antigen, T-Cell / immunology
  • Risk Factors
  • Signal Transduction
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / metabolism
  • Treatment Outcome

Substances

  • HLA Antigens
  • Isoantigens
  • Receptors, Antigen, T-Cell