Identification of an atypical CD8 T cell epitope encoded by murine cytomegalovirus ORF-M54 gaining dominance after deletion of the immunodominant antiviral CD8 T cell specificities.
Identifieur interne : 001521 ( PubMed/Checkpoint ); précédent : 001520; suivant : 001522Identification of an atypical CD8 T cell epitope encoded by murine cytomegalovirus ORF-M54 gaining dominance after deletion of the immunodominant antiviral CD8 T cell specificities.
Auteurs : Rafaela Holtappels [Allemagne] ; Niels A W. Lemmermann ; Doris Thomas ; Angélique Renzaho ; Matthias J. ReddehaseSource :
- Medical microbiology and immunology [ 1432-1831 ] ; 2015.
Descripteurs français
- KwdFr :
- Animaux, Antigène d'histocompatibilité H2-D (immunologie), Antigènes viraux (), Antigènes viraux (immunologie), Banque de peptides, Biologie informatique, Cadres ouverts de lecture (génétique), Cadres ouverts de lecture (immunologie), Cartographie épitopique, Cytotoxicité immunologique, Déterminants antigéniques des lymphocytes T (), Déterminants antigéniques des lymphocytes T (immunologie), Femelle, Génome viral, Infections à Herpesviridae (immunologie), Infections à Herpesviridae (virologie), Lymphocytes T CD8+ (immunologie), Muromegalovirus (génétique), Muromegalovirus (immunologie), Mutation, Peptides (), Peptides (immunologie), Souris, Séquence d'acides aminés, Épitopes immunodominants (), Épitopes immunodominants (immunologie).
- MESH :
- génétique : Cadres ouverts de lecture, Muromegalovirus.
- immunologie : Antigène d'histocompatibilité H2-D, Antigènes viraux, Cadres ouverts de lecture, Déterminants antigéniques des lymphocytes T, Infections à Herpesviridae, Lymphocytes T CD8+, Muromegalovirus, Peptides, Épitopes immunodominants.
- virologie : Infections à Herpesviridae.
- Animaux, Antigènes viraux, Banque de peptides, Biologie informatique, Cartographie épitopique, Cytotoxicité immunologique, Déterminants antigéniques des lymphocytes T, Femelle, Génome viral, Mutation, Peptides, Souris, Séquence d'acides aminés, Épitopes immunodominants.
English descriptors
- KwdEn :
- Amino Acid Sequence, Animals, Antigens, Viral (chemistry), Antigens, Viral (immunology), CD8-Positive T-Lymphocytes (immunology), Computational Biology, Cytotoxicity, Immunologic, Epitope Mapping, Epitopes, T-Lymphocyte (chemistry), Epitopes, T-Lymphocyte (immunology), Female, Genome, Viral, Herpesviridae Infections (immunology), Herpesviridae Infections (virology), Histocompatibility Antigen H-2D (immunology), Immunodominant Epitopes (chemistry), Immunodominant Epitopes (immunology), Mice, Muromegalovirus (genetics), Muromegalovirus (immunology), Mutation, Open Reading Frames (genetics), Open Reading Frames (immunology), Peptide Library, Peptides (chemistry), Peptides (immunology).
- MESH :
- chemical , chemistry : Antigens, Viral, Epitopes, T-Lymphocyte, Immunodominant Epitopes, Peptides.
- chemical , immunology : Antigens, Viral, Epitopes, T-Lymphocyte, Histocompatibility Antigen H-2D, Immunodominant Epitopes, Peptides.
- genetics : Muromegalovirus, Open Reading Frames.
- immunology : CD8-Positive T-Lymphocytes, Herpesviridae Infections, Muromegalovirus, Open Reading Frames.
- virology : Herpesviridae Infections.
- Amino Acid Sequence, Animals, Computational Biology, Cytotoxicity, Immunologic, Epitope Mapping, Female, Genome, Viral, Mice, Mutation, Peptide Library.
Abstract
Control of murine cytomegalovirus (mCMV) infection is mediated primarily by CD8 T cells, with four specificities dominating in BALB/c mice. Functional deletion of the respective immunodominant epitopes (IDEs) in mutant virus Δ4IDE revealed a still efficient control of infection. In a murine model of hematopoietic cell transplantation and infection with Δ4IDE, an mCMV-specific open reading frame (ORF) library screening assay indicated a strong CD8 T cell reactivity against the ORF-M54 product, the highly conserved and essential mCMV homolog of human CMV DNA polymerase UL54, which is a known inducer of in vivo protection against mCMV by DNA immunization. Applying bioinformatic algorithms for CD8 T cell epitope prediction, the top-scoring peptides were used to stimulate ex vivo-isolated CD8 T cells and to generate cytolytic T cell lines; yet, this approach failed to identify M54 epitope(s). As an alternative, a peptide library consisting of 549 10-mers with an offset of two amino acids (aa), covering the complete aa-sequence of the M54 protein, was synthesized and used for the stimulation. A region of 12 aa proved to encompass an epitope. An 'alanine walk' over this antigenic 12-mer and all possible 11-, 10- and 9-mers derived thereof revealed aa-residues critical for antigenicity, and terminal truncations identified the H-2D(d) presented 8-mer M5483-90 as the optimal epitope. An increased frequency of the corresponding CD8 T cells in the absence of the 4 IDEs indicated immunodomination by the IDE-specific CD8 T cells as a mechanism by which the generation of M54-specific CD8 T cells is inhibited after infection with wild-type mCMV.
DOI: 10.1007/s00430-015-0404-3
PubMed: 25805564
Affiliations:
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Functional deletion of the respective immunodominant epitopes (IDEs) in mutant virus Δ4IDE revealed a still efficient control of infection. In a murine model of hematopoietic cell transplantation and infection with Δ4IDE, an mCMV-specific open reading frame (ORF) library screening assay indicated a strong CD8 T cell reactivity against the ORF-M54 product, the highly conserved and essential mCMV homolog of human CMV DNA polymerase UL54, which is a known inducer of in vivo protection against mCMV by DNA immunization. Applying bioinformatic algorithms for CD8 T cell epitope prediction, the top-scoring peptides were used to stimulate ex vivo-isolated CD8 T cells and to generate cytolytic T cell lines; yet, this approach failed to identify M54 epitope(s). As an alternative, a peptide library consisting of 549 10-mers with an offset of two amino acids (aa), covering the complete aa-sequence of the M54 protein, was synthesized and used for the stimulation. A region of 12 aa proved to encompass an epitope. An 'alanine walk' over this antigenic 12-mer and all possible 11-, 10- and 9-mers derived thereof revealed aa-residues critical for antigenicity, and terminal truncations identified the H-2D(d) presented 8-mer M5483-90 as the optimal epitope. An increased frequency of the corresponding CD8 T cells in the absence of the 4 IDEs indicated immunodomination by the IDE-specific CD8 T cells as a mechanism by which the generation of M54-specific CD8 T cells is inhibited after infection with wild-type mCMV. </div></front></TEI><pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">25805564</PMID><DateCompleted><Year>2016</Year><Month>02</Month><Day>04</Day></DateCompleted><DateRevised><Year>2018</Year><Month>11</Month><Day>13</Day></DateRevised><Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">1432-1831</ISSN><JournalIssue CitedMedium="Internet"><Volume>204</Volume><Issue>3</Issue><PubDate><Year>2015</Year><Month>Jun</Month></PubDate></JournalIssue><Title>Medical microbiology and immunology</Title><ISOAbbreviation>Med. Microbiol. Immunol.</ISOAbbreviation></Journal><ArticleTitle>Identification of an atypical CD8 T cell epitope encoded by murine cytomegalovirus ORF-M54 gaining dominance after deletion of the immunodominant antiviral CD8 T cell specificities.</ArticleTitle><Pagination><MedlinePgn>317-26</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1007/s00430-015-0404-3</ELocationID><Abstract><AbstractText>Control of murine cytomegalovirus (mCMV) infection is mediated primarily by CD8 T cells, with four specificities dominating in BALB/c mice. Functional deletion of the respective immunodominant epitopes (IDEs) in mutant virus Δ4IDE revealed a still efficient control of infection. In a murine model of hematopoietic cell transplantation and infection with Δ4IDE, an mCMV-specific open reading frame (ORF) library screening assay indicated a strong CD8 T cell reactivity against the ORF-M54 product, the highly conserved and essential mCMV homolog of human CMV DNA polymerase UL54, which is a known inducer of in vivo protection against mCMV by DNA immunization. Applying bioinformatic algorithms for CD8 T cell epitope prediction, the top-scoring peptides were used to stimulate ex vivo-isolated CD8 T cells and to generate cytolytic T cell lines; yet, this approach failed to identify M54 epitope(s). As an alternative, a peptide library consisting of 549 10-mers with an offset of two amino acids (aa), covering the complete aa-sequence of the M54 protein, was synthesized and used for the stimulation. A region of 12 aa proved to encompass an epitope. An 'alanine walk' over this antigenic 12-mer and all possible 11-, 10- and 9-mers derived thereof revealed aa-residues critical for antigenicity, and terminal truncations identified the H-2D(d) presented 8-mer M5483-90 as the optimal epitope. An increased frequency of the corresponding CD8 T cells in the absence of the 4 IDEs indicated immunodomination by the IDE-specific CD8 T cells as a mechanism by which the generation of M54-specific CD8 T cells is inhibited after infection with wild-type mCMV. </AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Holtappels</LastName><ForeName>Rafaela</ForeName><Initials>R</Initials><AffiliationInfo><Affiliation>Institute for Virology and Research Center for Immunotherapy (FZI), University Medical Center of the Johannes Gutenberg-University Mainz, Obere Zahlbacher Strasse 67, Hochhaus am Augustusplatz, 55131, Mainz, Germany, r.holtappels@uni-mainz.de.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Lemmermann</LastName><ForeName>Niels A W</ForeName><Initials>NA</Initials></Author><Author ValidYN="Y"><LastName>Thomas</LastName><ForeName>Doris</ForeName><Initials>D</Initials></Author><Author ValidYN="Y"><LastName>Renzaho</LastName><ForeName>Angélique</ForeName><Initials>A</Initials></Author><Author ValidYN="Y"><LastName>Reddehase</LastName><ForeName>Matthias J</ForeName><Initials>MJ</Initials></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType><PublicationType UI="D013485">Research Support, Non-U.S. Gov't</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2015</Year><Month>03</Month><Day>25</Day></ArticleDate></Article><MedlineJournalInfo><Country>Germany</Country><MedlineTA>Med Microbiol Immunol</MedlineTA><NlmUniqueID>0314524</NlmUniqueID><ISSNLinking>0300-8584</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D000956">Antigens, Viral</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D018984">Epitopes, T-Lymphocyte</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D064532">Histocompatibility Antigen H-2D</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D016056">Immunodominant Epitopes</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D019151">Peptide Library</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D010455">Peptides</NameOfSubstance></Chemical></ChemicalList><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D000595" MajorTopicYN="N">Amino Acid Sequence</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D000818" MajorTopicYN="N">Animals</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D000956" MajorTopicYN="N">Antigens, Viral</DescriptorName><QualifierName UI="Q000737" MajorTopicYN="N">chemistry</QualifierName><QualifierName UI="Q000276" MajorTopicYN="N">immunology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D018414" MajorTopicYN="N">CD8-Positive T-Lymphocytes</DescriptorName><QualifierName UI="Q000276" MajorTopicYN="Y">immunology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D019295" MajorTopicYN="N">Computational Biology</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D003602" MajorTopicYN="N">Cytotoxicity, Immunologic</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D018604" MajorTopicYN="N">Epitope Mapping</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D018984" MajorTopicYN="N">Epitopes, T-Lymphocyte</DescriptorName><QualifierName UI="Q000737" MajorTopicYN="N">chemistry</QualifierName><QualifierName UI="Q000276" MajorTopicYN="Y">immunology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D005260" MajorTopicYN="N">Female</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D016679" MajorTopicYN="N">Genome, Viral</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D006566" MajorTopicYN="N">Herpesviridae Infections</DescriptorName><QualifierName UI="Q000276" MajorTopicYN="Y">immunology</QualifierName><QualifierName UI="Q000821" MajorTopicYN="N">virology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D064532" MajorTopicYN="N">Histocompatibility Antigen H-2D</DescriptorName><QualifierName UI="Q000276" MajorTopicYN="N">immunology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D016056" MajorTopicYN="N">Immunodominant Epitopes</DescriptorName><QualifierName UI="Q000737" MajorTopicYN="N">chemistry</QualifierName><QualifierName UI="Q000276" MajorTopicYN="Y">immunology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D051379" MajorTopicYN="N">Mice</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D018146" MajorTopicYN="N">Muromegalovirus</DescriptorName><QualifierName UI="Q000235" 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Lemmermann</name><name sortKey="Reddehase, Matthias J" sort="Reddehase, Matthias J" uniqKey="Reddehase M" first="Matthias J" last="Reddehase">Matthias J. Reddehase</name><name sortKey="Renzaho, Angelique" sort="Renzaho, Angelique" uniqKey="Renzaho A" first="Angélique" last="Renzaho">Angélique Renzaho</name><name sortKey="Thomas, Doris" sort="Thomas, Doris" uniqKey="Thomas D" first="Doris" last="Thomas">Doris Thomas</name></noCountry><country name="Allemagne"><noRegion><name sortKey="Holtappels, Rafaela" sort="Holtappels, Rafaela" uniqKey="Holtappels R" first="Rafaela" last="Holtappels">Rafaela Holtappels</name></noRegion></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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