Sequence homology between HLA-bound cytomegalovirus and human peptides: A potential trigger for alloreactivity

Authors

Charles E. Hall, Virginia Commonwealth University
Vishal N. Koparde, Virginia Commonwealth University
Maximilian Jameson-Lee, Virginia Commonwealth University
Abdelrhman G. Elnasseh, Virginia Commonwealth University
Allison F. Scalora, Virginia Commonwealth University
David J. Kobulnicky, Virginia Commonwealth University
Myrna G. Serrano, Virginia Commonwealth University
Catherine H. Roberts, Virginia Commonwealth University
Gregory A. Buck, Virginia Commonwealth University
Michael C. Neale, Virginia Commonwealth University
Daniel E. Nixon, Virginia Commonwealth University
Amir A. Toor, Virginia Commonwealth UniversityFollow

Document Type

Article

Original Publication Date

2017

Journal/Book/Conference Title

PLOS ONE

First Page

1

Last Page

23

DOI of Original Publication

10.1371/journal.pone.0178763

Comments

Originally published at https://doi.org/10.1371/journal.pone.0178763

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

Date of Submission

November 2017

Abstract

Human cytomegalovirus (hCMV) reactivation may often coincide with the development of graft-versus-host-disease (GVHD) in stem cell transplantation (SCT). Seventy seven SCT donor-recipient pairs (DRP) (HLA matched unrelated donor (MUD), n = 50; matched related donor (MRD), n = 27) underwent whole exome sequencing to identify single nucleotide polymorphisms (SNPs) generating alloreactive peptide libraries for each DRP (9-mer peptide-HLA complexes); Human CMV CROSS (Cross-Reactive Open Source Sequence) database was compiled from NCBI; HLA class I binding affinity for each DRPs HLA was calculated by NetMHCpan 2.8 and hCMV- derived 9-mers algorithmically compared to the alloreactive peptide-HLA complex libraries. Short consecutive (≥6) amino acid (AA) sequence homology matching hCMV to recipient peptides was considered for HLA-bound-peptide (IC50In silicoanalysis revealed multiple high affinity, immunogenic CMV-Human peptide matches (IC50<500 >nM) expressed in GVHD-affected tissue-specific manner. hCMV+GVHD was found in 18 patients, 13 developing hCMV viremia before GVHD onset. Analysis of patients with GVHD identified potential cross reactive peptide expression within affected organs. We propose that hCMV peptide sequence homology with human alloreactive peptides may contribute to the pathophysiology of GVHD.

Rights

© 2017 Hall et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Is Part Of

VCU Massey Cancer Center Publications