Gutenberg Open Science: Reconstitution of CD8 T cells protective against cytomegalovirus in a mouse model of hematopoietic cell transplantation : dynamics and inessentiality of epitope immunodominance

Please use this identifier to cite or link to this item: http://doi.org/10.25358/openscience-7854

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DC Field	Value	Language
dc.contributor.author	Holtappels, Rafaela	-
dc.contributor.author	Lemmermann, Niels	-
dc.contributor.author	Podlech, Jürgen	-
dc.contributor.author	Ebert, Stefan	-
dc.contributor.author	Reddehase, Matthias J.	-
dc.date.accessioned	2022-10-05T09:34:01Z	-
dc.date.available	2022-10-05T09:34:01Z	-
dc.date.issued	2016
dc.identifier.uri	https://openscience.ub.uni-mainz.de/handle/20.500.12030/7869	-
dc.description.abstract	Successful reconstitution of cytomegalovirus (CMV)-specific CD8+ T cells by hematopoietic cell transplantation (HCT) gives a favorable prognosis for the control of CMV reactivation and prevention of CMV disease after hematoablative therapy of hematopoietic malignancies. In the transient immunocompromised state after HCT, pre-emptive cytoimmunotherapy with viral epitope-specific effector or memory CD8+ T cells is a promising option to speed up antiviral control. Despite high-coding capacity of CMVs and a broad CD8+ T-cell response on the population level, which reflects polymorphism in major histocompatibility complex class-I (MHC-I) glycoproteins, the response in terms of quantity of CD8+ T cells in any individual is directed against a limited set of CMV-encoded epitopes selected for presentation by the private repertoire of MHC-I molecules. Such epitopes are known as “immunodominant” epitopes (IDEs). Besides host immunogenetics, genetic variance in CMV strains harbored as latent viruses by an individual HCT recipient can also determine the set of IDEs, which complicates a “personalized immunotherapy.” It is, therefore, an important question if IDE-specific CD8+ T-cell reconstitution after HCT is critical or dispensable for antiviral control. As viruses with targeted mutations of IDEs cannot be experimentally tested in HCT patients, we employed the well-established mouse model of HCT. Notably, control of murine CMV (mCMV) after HCT was comparably efficient for IDE-deletion mutant mCMV-Δ4IDE and the corresponding IDE-expressing revertant virus mCMV-Δ4IDE-rev. Thus, antigenicity-loss mutations in IDEs do not result in loss-of-function of a polyclonal CD8+ T-cell population. Although IDE deletion was not associated with global changes in the response to non-IDE epitopes, the collective of non-IDE-specific CD8+ T-cells infiltrates infected tissue and confines infection within nodular inflammatory foci. We conclude from the model, and predict also for human CMV, that there is no need to exclusively aim for IDE-specific immunoreconstitution.	en_GB
dc.description.sponsorship	DFG, Open Access-Publizieren Universität Mainz / Universitätsmedizin	de
dc.language.iso	eng	de
dc.rights	CC BY	*
dc.rights.uri	https://creativecommons.org/licenses/by/4.0/	*
dc.subject.ddc	610 Medizin	de_DE
dc.subject.ddc	610 Medical sciences	en_GB
dc.title	Reconstitution of CD8 T cells protective against cytomegalovirus in a mouse model of hematopoietic cell transplantation : dynamics and inessentiality of epitope immunodominance	en_GB
dc.type	Zeitschriftenaufsatz	de
dc.identifier.doi	http://doi.org/10.25358/openscience-7854	-
jgu.type.dinitype	article	en_GB
jgu.type.version	Published version	de
jgu.type.resource	Text	de
jgu.organisation.department	FB 04 Medizin	de
jgu.organisation.number	2700	-
jgu.organisation.name	Johannes Gutenberg-Universität Mainz	-
jgu.rights.accessrights	openAccess	-
jgu.journal.title	Frontiers in immunology	de
jgu.journal.volume	7	de
jgu.pages.alternative	Art. 232	de
jgu.publisher.year	2016	-
jgu.publisher.name	Frontiers Media	de
jgu.publisher.place	Lausanne	de
jgu.publisher.uri	http://dx.doi.org/10.3389/fimmu.2016.00232	de
jgu.publisher.issn	1664-3224	de
jgu.organisation.place	Mainz	-
jgu.subject.ddccode	610	de
opus.date.modified	2018-08-23T08:27:40Z
opus.subject.dfgcode	00-000
opus.organisation.string	FB 04: Medizin: Institut für Virologie	de_DE
opus.identifier.opusid	56366
opus.institute.number	0409
opus.metadataonly	false
opus.type.contenttype	Keine	de_DE
opus.type.contenttype	None	en_EN
opus.affiliated	Holtappels, Rafaela
opus.affiliated	Lemmermann, Niels
opus.affiliated	Podlech, Jürgen
opus.affiliated	Reddehase, Matthias J.
jgu.publisher.doi	10.3389/fimmu.2016.00232	de
jgu.organisation.ror	https://ror.org/023b0x485	-
Appears in collections:	DFG-OA-Publizieren (2012 - 2017)

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