High Throughput Human T Cell Receptor Sequencing: A New Window Into Repertoire Establishment and Alloreactivity
Abstract
Recent advances in high throughput sequencing (HTS) of T cell receptors (TCRs) and in transcriptomic analysis, particularly at the single cell level, have opened the door to a new level of understanding of human immunology and immune-related diseases. In this article, we discuss the use of HTS of TCRs to discern the factors controlling human T cell repertoire development and how this approach can be used in combination with human immune system (HIS) mouse models to understand human repertoire selection in an unprecedented manner. An exceptionally high proportion of human T cells has alloreactive potential, which can best be understood as a consequence of the processes governing thymic selection. High throughput TCR sequencing has allowed assessment of the development, magnitude and nature of the human alloresponse at a new level and has provided a tool for tracking the fate of pre-transplant-defined donor- and host-reactive TCRs following transplantation. New insights into human allograft rejection and tolerance obtained with this method in combination with single cell transcriptional analyses are reviewed here.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Nov 05, 2021
- Source ID
- 10.3389/fimmu.2021.777756
Entities
People
- Jianing Fu
- Megan Sykes
- Mohsen Khosravi-maharlooei
Organizations
- American Diabetes Association
- American Society of Transplantation
- Columbia University
- National Center for Advancing Translational Sciences
- National Institute of Allergy and Infectious Diseases
- National Institute of Diabetes and Digestive and Kidney Diseases
- United States Department of Defense