T Cell Alloreactivity and Organ Transplant Risk Stratification Models Using High-Resolution HLA and Genomic Data

University Of California, San Diego, La Jolla CA

Investigators

Abstract

The conventional focus for histocompatibility in clinical solid organ transplantation focuses on humeral immunity, avoiding donor HLA molecules against which the recipient has pre-existing alloantibodies capable of mediating hyperacute rejection. While this is a practical approach mitigating some immunologic risk based on clinically available information, it does not address the inherent risks of T cell alloreactivity, which is a significant contributor to allograft rejection and requires life-long immunosuppression. In this proposal, we will leverage sequencing technologies and approaches adapted from immune-oncology to identify HLA allele-specific factors in solid organ transplant donors and recipients driving T cell alloimmune responses. We will develop a computational algorithm, CHART, to predict donor/recipient pair-specific T cell alloreactivity and risk of solid organ transplant rejection, with the goal toward precision medicine approaches for histocompatibility and personalized immunosuppression.