Dynamical System Modeling to Simulate Donor T Cell Response to Whole Exome Sequencing-Derived Recipient Peptides: Understanding Randomness in Clinical Outcomes Following Stem Cell Transplantation

Abstract

Alloreactivity following stem cell transplantation (SCT) is difficult to predict in patients undergoing transplantation from HLA matched donors. In this study we performed whole exome sequencing of SCT donor-recipient pairs (DRP). This allowed determination of entire library of alloreactive peptide sequences which would bind HLA class I molecules in each DRP. Utilizing the HLA binding affinity (IC50) and tissue expression levels of the parent proteins, an aggregate donor T cell response to the recipient alloreactive peptides was calculated using a vector-operator dynamical system model. Marked variability in the simulated CD8+ T cell responses was observed in all the donor recipient pairs.