Noncanonical Expression of a Murine Cytomegalovirus Early Protein CD8 T-Cell Epitope as an Immediate Early Epitope Based on Transcription from an Upstream Gene
Viral CD8 T-cell epitopes, represented by viral peptides bound to major histocompatibility complex class-I (MHC-I) glycoproteins, are often identified by “reverse immunology”, a strategy not requiring biochemical and structural knowledge of the actual viral protein from which they are derived by ant...
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doaj-e8afdfcd268a44c88fd6c3a3a2f014592020-11-25T02:41:36ZengMDPI AGViruses1999-49152014-02-016280883110.3390/v6020808v6020808Noncanonical Expression of a Murine Cytomegalovirus Early Protein CD8 T-Cell Epitope as an Immediate Early Epitope Based on Transcription from an Upstream GeneAnnette Fink0Julia K. Büttner1Doris Thomas2Rafaela Holtappels3Matthias J. Reddehase4Niels A. W. Lemmermann5Institute for Virology and Research Center for Immunology (FZI), University Medical Center of the Johannes Gutenberg-University Mainz, Obere Zahlbacher Str. 67, Mainz D-55131, GermanyInstitute for Virology and Research Center for Immunology (FZI), University Medical Center of the Johannes Gutenberg-University Mainz, Obere Zahlbacher Str. 67, Mainz D-55131, GermanyInstitute for Virology and Research Center for Immunology (FZI), University Medical Center of the Johannes Gutenberg-University Mainz, Obere Zahlbacher Str. 67, Mainz D-55131, GermanyInstitute for Virology and Research Center for Immunology (FZI), University Medical Center of the Johannes Gutenberg-University Mainz, Obere Zahlbacher Str. 67, Mainz D-55131, GermanyInstitute for Virology and Research Center for Immunology (FZI), University Medical Center of the Johannes Gutenberg-University Mainz, Obere Zahlbacher Str. 67, Mainz D-55131, GermanyInstitute for Virology and Research Center for Immunology (FZI), University Medical Center of the Johannes Gutenberg-University Mainz, Obere Zahlbacher Str. 67, Mainz D-55131, GermanyViral CD8 T-cell epitopes, represented by viral peptides bound to major histocompatibility complex class-I (MHC-I) glycoproteins, are often identified by “reverse immunology”, a strategy not requiring biochemical and structural knowledge of the actual viral protein from which they are derived by antigen processing. Instead, bioinformatic algorithms predicting the probability of C-terminal cleavage in the proteasome, as well as binding affinity to the presenting MHC-I molecules, are applied to amino acid sequences deduced from predicted open reading frames (ORFs) based on the genomic sequence. If the protein corresponding to an antigenic ORF is known, it is usually inferred that the kinetic class of the protein also defines the phase in the viral replicative cycle during which the respective antigenic peptide is presented for recognition by CD8 T cells. We have previously identified a nonapeptide from the predicted ORFm164 of murine cytomegalovirus that is presented by the MHC-I allomorph H-2 Dd and that is immunodominant in BALB/c (H-2d haplotype) mice. Surprisingly, although the ORFm164 protein gp36.5 is expressed as an Early (E) phase protein, the m164 epitope is presented already during the Immediate Early (IE) phase, based on the expression of an upstream mRNA starting within ORFm167 and encompassing ORFm164.http://www.mdpi.com/1999-4915/6/2/808antigenic peptidesantigen presentationCD8 T cell epitopegene expressionimmediate-early proteinmurine CMV ORF m164open reading frameRACE mappingreverse immunologytranscription start sitetranslation start site |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Annette Fink Julia K. Büttner Doris Thomas Rafaela Holtappels Matthias J. Reddehase Niels A. W. Lemmermann |
spellingShingle |
Annette Fink Julia K. Büttner Doris Thomas Rafaela Holtappels Matthias J. Reddehase Niels A. W. Lemmermann Noncanonical Expression of a Murine Cytomegalovirus Early Protein CD8 T-Cell Epitope as an Immediate Early Epitope Based on Transcription from an Upstream Gene Viruses antigenic peptides antigen presentation CD8 T cell epitope gene expression immediate-early protein murine CMV ORF m164 open reading frame RACE mapping reverse immunology transcription start site translation start site |
author_facet |
Annette Fink Julia K. Büttner Doris Thomas Rafaela Holtappels Matthias J. Reddehase Niels A. W. Lemmermann |
author_sort |
Annette Fink |
title |
Noncanonical Expression of a Murine Cytomegalovirus Early Protein CD8 T-Cell Epitope as an Immediate Early Epitope Based on Transcription from an Upstream Gene |
title_short |
Noncanonical Expression of a Murine Cytomegalovirus Early Protein CD8 T-Cell Epitope as an Immediate Early Epitope Based on Transcription from an Upstream Gene |
title_full |
Noncanonical Expression of a Murine Cytomegalovirus Early Protein CD8 T-Cell Epitope as an Immediate Early Epitope Based on Transcription from an Upstream Gene |
title_fullStr |
Noncanonical Expression of a Murine Cytomegalovirus Early Protein CD8 T-Cell Epitope as an Immediate Early Epitope Based on Transcription from an Upstream Gene |
title_full_unstemmed |
Noncanonical Expression of a Murine Cytomegalovirus Early Protein CD8 T-Cell Epitope as an Immediate Early Epitope Based on Transcription from an Upstream Gene |
title_sort |
noncanonical expression of a murine cytomegalovirus early protein cd8 t-cell epitope as an immediate early epitope based on transcription from an upstream gene |
publisher |
MDPI AG |
series |
Viruses |
issn |
1999-4915 |
publishDate |
2014-02-01 |
description |
Viral CD8 T-cell epitopes, represented by viral peptides bound to major histocompatibility complex class-I (MHC-I) glycoproteins, are often identified by “reverse immunology”, a strategy not requiring biochemical and structural knowledge of the actual viral protein from which they are derived by antigen processing. Instead, bioinformatic algorithms predicting the probability of C-terminal cleavage in the proteasome, as well as binding affinity to the presenting MHC-I molecules, are applied to amino acid sequences deduced from predicted open reading frames (ORFs) based on the genomic sequence. If the protein corresponding to an antigenic ORF is known, it is usually inferred that the kinetic class of the protein also defines the phase in the viral replicative cycle during which the respective antigenic peptide is presented for recognition by CD8 T cells. We have previously identified a nonapeptide from the predicted ORFm164 of murine cytomegalovirus that is presented by the MHC-I allomorph H-2 Dd and that is immunodominant in BALB/c (H-2d haplotype) mice. Surprisingly, although the ORFm164 protein gp36.5 is expressed as an Early (E) phase protein, the m164 epitope is presented already during the Immediate Early (IE) phase, based on the expression of an upstream mRNA starting within ORFm167 and encompassing ORFm164. |
topic |
antigenic peptides antigen presentation CD8 T cell epitope gene expression immediate-early protein murine CMV ORF m164 open reading frame RACE mapping reverse immunology transcription start site translation start site |
url |
http://www.mdpi.com/1999-4915/6/2/808 |
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