Document Type

Article

Original Publication Date

2018

Journal/Book/Conference Title

Frontiers in Immunology

Volume

9:2284

First Page

1

Last Page

18

DOI of Original Publication

10.3389/fimmu.2018.02284

Comments

Originally published at https://doi.org/10.3389/fimmu.2018.02284

Funded in part by the VCU Libraries Open Access Publishing Fund.

Date of Submission

October 2019

Abstract

Alloreactivity compromising clinical outcomes in stem cell transplantation is observed despite HLA matching of donors and recipients. This has its origin in the variation between the exomes of the two, which provides the basis for minor histocompatibility antigens (mHA). The mHA presented on the HLA class I and II molecules and the ensuing T cell response to these antigens results in graft vs. host disease. In this paper, results of a whole exome sequencing study are presented, with resulting alloreactive polymorphic peptides and their HLA class I and HLA class II (DRB1) binding affinity quantified. Large libraries of potentially alloreactive recipient peptides binding both sets of molecules were identified, with HLA-DRB1 generally presenting a greater number of peptides. These results are used to develop a quantitative framework to understand the immunobiology of transplantation. A tensor-based approach is used to derive the equations needed to determine the alloreactive donor T cell response from the mHA-HLA binding affinity and protein expression data. This approach may be used in future studies to simulate the magnitude of expected donor T cell response and determine the risk for alloreactive complications in HLA matched or mismatched hematopoietic cell and solid organ transplantation.

Rights

Copyright © 2018 Salman, Koparde, Hall, Jameson-Lee, Roberts, Serrano, AbdulRazzaq, Meier, Kennedy, Manjili, Spellman, Wijesinghe, Hashmi, Buck, Qayyum, Neale, Reed and Toor. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

Is Part Of

VCU Massey Cancer Center Publications

Download

Share

COinS