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 : 001074 ( Ncbi/Checkpoint ); précédent : 001073; suivant : 001075Identification 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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pubmed:25805564Le document en format XML
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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><affiliations><list><country><li>Allemagne</li></country></list><tree><noCountry><name sortKey="Lemmermann, Niels A W" sort="Lemmermann, Niels A W" uniqKey="Lemmermann N" first="Niels A W" last="Lemmermann">Niels A W. 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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