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Sequence homology between HLA-bound cytomegalovirus and human peptides: A potential trigger for alloreactivity
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 exo...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5553991/ https://www.ncbi.nlm.nih.gov/pubmed/28800601 http://dx.doi.org/10.1371/journal.pone.0178763 |
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author | Hall, Charles E. Koparde, Vishal N. Jameson-Lee, Maximilian Elnasseh, Abdelrhman G. Scalora, Allison F. Kobulnicky, David J. Serrano, Myrna G. Roberts, Catherine H. Buck, Gregory A. Neale, Michael C. Nixon, Daniel E. Toor, Amir A. |
author_facet | Hall, Charles E. Koparde, Vishal N. Jameson-Lee, Maximilian Elnasseh, Abdelrhman G. Scalora, Allison F. Kobulnicky, David J. Serrano, Myrna G. Roberts, Catherine H. Buck, Gregory A. Neale, Michael C. Nixon, Daniel E. Toor, Amir A. |
author_sort | Hall, Charles E. |
collection | PubMed |
description | 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 (IC50<500nM) cross reactivity. Of the 70,686 hCMV 9-mers contained within the hCMV CROSS database, an average of 29,658 matched the MRD DRP alloreactive peptides and 52,910 matched MUD DRP peptides (p<0.001). In silico analysis 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. |
format | Online Article Text |
id | pubmed-5553991 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-55539912017-08-25 Sequence homology between HLA-bound cytomegalovirus and human peptides: A potential trigger for alloreactivity Hall, Charles E. Koparde, Vishal N. Jameson-Lee, Maximilian Elnasseh, Abdelrhman G. Scalora, Allison F. Kobulnicky, David J. Serrano, Myrna G. Roberts, Catherine H. Buck, Gregory A. Neale, Michael C. Nixon, Daniel E. Toor, Amir A. PLoS One Research Article 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 (IC50<500nM) cross reactivity. Of the 70,686 hCMV 9-mers contained within the hCMV CROSS database, an average of 29,658 matched the MRD DRP alloreactive peptides and 52,910 matched MUD DRP peptides (p<0.001). In silico analysis 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. Public Library of Science 2017-08-11 /pmc/articles/PMC5553991/ /pubmed/28800601 http://dx.doi.org/10.1371/journal.pone.0178763 Text en © 2017 Hall et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Hall, Charles E. Koparde, Vishal N. Jameson-Lee, Maximilian Elnasseh, Abdelrhman G. Scalora, Allison F. Kobulnicky, David J. Serrano, Myrna G. Roberts, Catherine H. Buck, Gregory A. Neale, Michael C. Nixon, Daniel E. Toor, Amir A. Sequence homology between HLA-bound cytomegalovirus and human peptides: A potential trigger for alloreactivity |
title | Sequence homology between HLA-bound cytomegalovirus and human peptides: A potential trigger for alloreactivity |
title_full | Sequence homology between HLA-bound cytomegalovirus and human peptides: A potential trigger for alloreactivity |
title_fullStr | Sequence homology between HLA-bound cytomegalovirus and human peptides: A potential trigger for alloreactivity |
title_full_unstemmed | Sequence homology between HLA-bound cytomegalovirus and human peptides: A potential trigger for alloreactivity |
title_short | Sequence homology between HLA-bound cytomegalovirus and human peptides: A potential trigger for alloreactivity |
title_sort | sequence homology between hla-bound cytomegalovirus and human peptides: a potential trigger for alloreactivity |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5553991/ https://www.ncbi.nlm.nih.gov/pubmed/28800601 http://dx.doi.org/10.1371/journal.pone.0178763 |
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