title: A New Window into the Human Alloresponse.
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.
authors.affiliation: 1 Columbia Center for Translational Immunology, Columbia University Medical Center, New York, NY.2 Departments of Systems Biology and Biomedical Informatics, Columbia University Medical Center, New York, NY.
authors.forename: Susan
authors.initials: S
authors.lastname: DeWolf
authors.forename: Yufeng
authors.initials: Y
authors.lastname: Shen
authors.forename: Megan
authors.initials: M
authors.lastname: Sykes
mesh_terms: D064591:Allografts; D000818:Animals; D006084:Graft Rejection / Q000097:blood / Q000175:diagnosis* / Q000276:immunology; D006085:Graft Survival; D006680:HLA Antigens / Q000097:blood / Q000276:immunology*; D059014:High-Throughput Nucleotide Sequencing; D006648:Histocompatibility; D006650:Histocompatibility Testing / Q000379:methods*; D006801:Humans; D007519:Isoantigens / Q000097:blood / Q000276:immunology*; D008213:Lymphocyte Activation; D007959:Lymphocyte Culture Test, Mixed; D016377:Organ Transplantation / Q000009:adverse effects*; D010641:Phenotype; D011237:Predictive Value of Tests; D011948:Receptors, Antigen, T-Cell / Q000235:genetics* / Q000276:immunology; D012307:Risk Factors; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D016896:Treatment Outcome
chemical_list: D006680:HLA Antigens; D007519:Isoantigens; D011948:Receptors, Antigen, T-Cell