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

TL;DR

This study models donor T cell responses to recipient peptides derived from whole exome sequencing to understand the variability and unpredictability of clinical outcomes after stem cell transplantation.

Contribution

It introduces a dynamical system model that simulates T cell responses based on sequencing data, providing insights into the randomness of transplant outcomes.

Findings

Marked variability in simulated T cell responses across pairs

The model links peptide binding affinity and tissue expression to immune response

Potential to predict transplant success based on sequence data

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.