Identification and HLA-tetramer-validation of human CD4+ and CD8+ T cell responses against CMV proteins IE1 and IE2

Autores
Braendstrup, Peter; Mortensen, Bo Kok; Justesen, Sune; Østerby, Thomas; Rasmussen, Michael; Hansen, Andreas Martin; Christiansen, Claus Bohn; Hansen, Morten Bagge; Nielsen, Morten; Vindeløv, Lars; Buus, Søren; Stryhn, Anette
Año de publicación
2014
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Human cytomegalovirus (HCMV) is an important human pathogen. It is a leading cause of congenital infection and a leading infectious threat to recipients of solid organ transplants as well as of allogeneic hematopoietic cell transplants. Moreover, it has recently been suggested that HCMV may promote tumor development. Both CD4+ and CD8+ T cell responses are important for long-term control of the virus, and adoptive transfer of HCMV-specific T cells has led to protection from reactivation and HCMV disease. Identification of HCMV-specific T cell epitopes has primarily focused on CD8+ T cell responses against the pp65 phosphoprotein. In this study, we have focused on CD4+ and CD8+ T cell responses against the immediate early 1 and 2 proteins (IE1 and IE2). Using overlapping peptides spanning the entire IE1 and IE2 sequences, peripheral blood mononuclear cells from 16 healthy, HLA-typed, donors were screened by ex vivo IFN-γ ELISpot and in vitro intracellular cytokine secretion assays. The specificities of CD4+ and CD8+ T cell responses were identified and validated by HLA class II and I tetramers, respectively. Eighty-one CD4+ and 44 CD8+ T cell responses were identified representing at least seven different CD4 epitopes and 14 CD8 epitopes restricted by seven and 11 different HLA class II and I molecules, respectively, in total covering 91 and 98% of the Caucasian population, respectively. Presented in the context of several different HLA class II molecules, two epitope areas in IE1 and IE2 were recognized in about half of the analyzed donors. These data may be used to design a versatile anti-HCMV vaccine and/or immunotherapy strategy.
Fil: Braendstrup, Peter. Universidad de Copenhagen; Dinamarca
Fil: Mortensen, Bo Kok. Universidad de Copenhagen; Dinamarca
Fil: Justesen, Sune. Universidad de Copenhagen; Dinamarca
Fil: Østerby, Thomas. Universidad de Copenhagen; Dinamarca
Fil: Rasmussen, Michael. Universidad de Copenhagen; Dinamarca
Fil: Hansen, Andreas Martin. Universidad de Copenhagen; Dinamarca
Fil: Christiansen, Claus Bohn. Copenhagen University Hospital; Dinamarca
Fil: Hansen, Morten Bagge. Copenhagen University Hospital; Dinamarca
Fil: Nielsen, Morten. Technical University of Denmark; Dinamarca. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas; Argentina
Fil: Vindeløv, Lars. Copenhagen University Hospital; Dinamarca
Fil: Buus, Søren. Universidad de Copenhagen; Dinamarca
Fil: Stryhn, Anette. Universidad de Copenhagen; Dinamarca
Materia
T cell epitope
Tetramers
Binding prediction
Miminal epitopes
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/17981
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/17981
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Identification and HLA-tetramer-validation of human CD4+ and CD8+ T cell responses against CMV proteins IE1 and IE2Braendstrup, PeterMortensen, Bo KokJustesen, SuneØsterby, ThomasRasmussen, MichaelHansen, Andreas MartinChristiansen, Claus BohnHansen, Morten BaggeNielsen, MortenVindeløv, LarsBuus, SørenStryhn, AnetteT cell epitopeTetramersBinding predictionMiminal epitopeshttps://purl.org/becyt/ford/3.3https://purl.org/becyt/ford/3Human cytomegalovirus (HCMV) is an important human pathogen. It is a leading cause of congenital infection and a leading infectious threat to recipients of solid organ transplants as well as of allogeneic hematopoietic cell transplants. Moreover, it has recently been suggested that HCMV may promote tumor development. Both CD4+ and CD8+ T cell responses are important for long-term control of the virus, and adoptive transfer of HCMV-specific T cells has led to protection from reactivation and HCMV disease. Identification of HCMV-specific T cell epitopes has primarily focused on CD8+ T cell responses against the pp65 phosphoprotein. In this study, we have focused on CD4+ and CD8+ T cell responses against the immediate early 1 and 2 proteins (IE1 and IE2). Using overlapping peptides spanning the entire IE1 and IE2 sequences, peripheral blood mononuclear cells from 16 healthy, HLA-typed, donors were screened by ex vivo IFN-γ ELISpot and in vitro intracellular cytokine secretion assays. The specificities of CD4+ and CD8+ T cell responses were identified and validated by HLA class II and I tetramers, respectively. Eighty-one CD4+ and 44 CD8+ T cell responses were identified representing at least seven different CD4 epitopes and 14 CD8 epitopes restricted by seven and 11 different HLA class II and I molecules, respectively, in total covering 91 and 98% of the Caucasian population, respectively. Presented in the context of several different HLA class II molecules, two epitope areas in IE1 and IE2 were recognized in about half of the analyzed donors. These data may be used to design a versatile anti-HCMV vaccine and/or immunotherapy strategy.Fil: Braendstrup, Peter. Universidad de Copenhagen; DinamarcaFil: Mortensen, Bo Kok. Universidad de Copenhagen; DinamarcaFil: Justesen, Sune. Universidad de Copenhagen; DinamarcaFil: Østerby, Thomas. Universidad de Copenhagen; DinamarcaFil: Rasmussen, Michael. Universidad de Copenhagen; DinamarcaFil: Hansen, Andreas Martin. Universidad de Copenhagen; DinamarcaFil: Christiansen, Claus Bohn. Copenhagen University Hospital; DinamarcaFil: Hansen, Morten Bagge. Copenhagen University Hospital; DinamarcaFil: Nielsen, Morten. Technical University of Denmark; Dinamarca. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas; ArgentinaFil: Vindeløv, Lars. Copenhagen University Hospital; DinamarcaFil: Buus, Søren. Universidad de Copenhagen; DinamarcaFil: Stryhn, Anette. Universidad de Copenhagen; DinamarcaPublic Library of Science2014-04info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/17981Braendstrup, Peter; Mortensen, Bo Kok; Justesen, Sune; Østerby, Thomas; Rasmussen, Michael; et al.; Identification and HLA-tetramer-validation of human CD4+ and CD8+ T cell responses against CMV proteins IE1 and IE2; Public Library of Science; Plos One; 9; 4; 4-2014; 1-12; e948921932-6203enginfo:eu-repo/semantics/altIdentifier/url/http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0094892info:eu-repo/semantics/altIdentifier/doi/10.1371/journal.pone.0094892info:eu-repo/semantics/altIdentifier/url/https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24760079/info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T09:43:05Zoai:ri.conicet.gov.ar:11336/17981instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-29 09:43:05.7CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Identification and HLA-tetramer-validation of human CD4+ and CD8+ T cell responses against CMV proteins IE1 and IE2
title Identification and HLA-tetramer-validation of human CD4+ and CD8+ T cell responses against CMV proteins IE1 and IE2
spellingShingle Identification and HLA-tetramer-validation of human CD4+ and CD8+ T cell responses against CMV proteins IE1 and IE2
Braendstrup, Peter
T cell epitope
Tetramers
Binding prediction
Miminal epitopes
title_short Identification and HLA-tetramer-validation of human CD4+ and CD8+ T cell responses against CMV proteins IE1 and IE2
title_full Identification and HLA-tetramer-validation of human CD4+ and CD8+ T cell responses against CMV proteins IE1 and IE2
title_fullStr Identification and HLA-tetramer-validation of human CD4+ and CD8+ T cell responses against CMV proteins IE1 and IE2
title_full_unstemmed Identification and HLA-tetramer-validation of human CD4+ and CD8+ T cell responses against CMV proteins IE1 and IE2
title_sort Identification and HLA-tetramer-validation of human CD4+ and CD8+ T cell responses against CMV proteins IE1 and IE2
dc.creator.none.fl_str_mv Braendstrup, Peter
Mortensen, Bo Kok
Justesen, Sune
Østerby, Thomas
Rasmussen, Michael
Hansen, Andreas Martin
Christiansen, Claus Bohn
Hansen, Morten Bagge
Nielsen, Morten
Vindeløv, Lars
Buus, Søren
Stryhn, Anette
author Braendstrup, Peter
author_facet Braendstrup, Peter
Mortensen, Bo Kok
Justesen, Sune
Østerby, Thomas
Rasmussen, Michael
Hansen, Andreas Martin
Christiansen, Claus Bohn
Hansen, Morten Bagge
Nielsen, Morten
Vindeløv, Lars
Buus, Søren
Stryhn, Anette
author_role author
author2 Mortensen, Bo Kok
Justesen, Sune
Østerby, Thomas
Rasmussen, Michael
Hansen, Andreas Martin
Christiansen, Claus Bohn
Hansen, Morten Bagge
Nielsen, Morten
Vindeløv, Lars
Buus, Søren
Stryhn, Anette
author2_role author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv T cell epitope
Tetramers
Binding prediction
Miminal epitopes
topic T cell epitope
Tetramers
Binding prediction
Miminal epitopes
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.3
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Human cytomegalovirus (HCMV) is an important human pathogen. It is a leading cause of congenital infection and a leading infectious threat to recipients of solid organ transplants as well as of allogeneic hematopoietic cell transplants. Moreover, it has recently been suggested that HCMV may promote tumor development. Both CD4+ and CD8+ T cell responses are important for long-term control of the virus, and adoptive transfer of HCMV-specific T cells has led to protection from reactivation and HCMV disease. Identification of HCMV-specific T cell epitopes has primarily focused on CD8+ T cell responses against the pp65 phosphoprotein. In this study, we have focused on CD4+ and CD8+ T cell responses against the immediate early 1 and 2 proteins (IE1 and IE2). Using overlapping peptides spanning the entire IE1 and IE2 sequences, peripheral blood mononuclear cells from 16 healthy, HLA-typed, donors were screened by ex vivo IFN-γ ELISpot and in vitro intracellular cytokine secretion assays. The specificities of CD4+ and CD8+ T cell responses were identified and validated by HLA class II and I tetramers, respectively. Eighty-one CD4+ and 44 CD8+ T cell responses were identified representing at least seven different CD4 epitopes and 14 CD8 epitopes restricted by seven and 11 different HLA class II and I molecules, respectively, in total covering 91 and 98% of the Caucasian population, respectively. Presented in the context of several different HLA class II molecules, two epitope areas in IE1 and IE2 were recognized in about half of the analyzed donors. These data may be used to design a versatile anti-HCMV vaccine and/or immunotherapy strategy.
Fil: Braendstrup, Peter. Universidad de Copenhagen; Dinamarca
Fil: Mortensen, Bo Kok. Universidad de Copenhagen; Dinamarca
Fil: Justesen, Sune. Universidad de Copenhagen; Dinamarca
Fil: Østerby, Thomas. Universidad de Copenhagen; Dinamarca
Fil: Rasmussen, Michael. Universidad de Copenhagen; Dinamarca
Fil: Hansen, Andreas Martin. Universidad de Copenhagen; Dinamarca
Fil: Christiansen, Claus Bohn. Copenhagen University Hospital; Dinamarca
Fil: Hansen, Morten Bagge. Copenhagen University Hospital; Dinamarca
Fil: Nielsen, Morten. Technical University of Denmark; Dinamarca. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas; Argentina
Fil: Vindeløv, Lars. Copenhagen University Hospital; Dinamarca
Fil: Buus, Søren. Universidad de Copenhagen; Dinamarca
Fil: Stryhn, Anette. Universidad de Copenhagen; Dinamarca
description Human cytomegalovirus (HCMV) is an important human pathogen. It is a leading cause of congenital infection and a leading infectious threat to recipients of solid organ transplants as well as of allogeneic hematopoietic cell transplants. Moreover, it has recently been suggested that HCMV may promote tumor development. Both CD4+ and CD8+ T cell responses are important for long-term control of the virus, and adoptive transfer of HCMV-specific T cells has led to protection from reactivation and HCMV disease. Identification of HCMV-specific T cell epitopes has primarily focused on CD8+ T cell responses against the pp65 phosphoprotein. In this study, we have focused on CD4+ and CD8+ T cell responses against the immediate early 1 and 2 proteins (IE1 and IE2). Using overlapping peptides spanning the entire IE1 and IE2 sequences, peripheral blood mononuclear cells from 16 healthy, HLA-typed, donors were screened by ex vivo IFN-γ ELISpot and in vitro intracellular cytokine secretion assays. The specificities of CD4+ and CD8+ T cell responses were identified and validated by HLA class II and I tetramers, respectively. Eighty-one CD4+ and 44 CD8+ T cell responses were identified representing at least seven different CD4 epitopes and 14 CD8 epitopes restricted by seven and 11 different HLA class II and I molecules, respectively, in total covering 91 and 98% of the Caucasian population, respectively. Presented in the context of several different HLA class II molecules, two epitope areas in IE1 and IE2 were recognized in about half of the analyzed donors. These data may be used to design a versatile anti-HCMV vaccine and/or immunotherapy strategy.
publishDate 2014
dc.date.none.fl_str_mv 2014-04
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/17981
Braendstrup, Peter; Mortensen, Bo Kok; Justesen, Sune; Østerby, Thomas; Rasmussen, Michael; et al.; Identification and HLA-tetramer-validation of human CD4+ and CD8+ T cell responses against CMV proteins IE1 and IE2; Public Library of Science; Plos One; 9; 4; 4-2014; 1-12; e94892
1932-6203
url http://hdl.handle.net/11336/17981
identifier_str_mv Braendstrup, Peter; Mortensen, Bo Kok; Justesen, Sune; Østerby, Thomas; Rasmussen, Michael; et al.; Identification and HLA-tetramer-validation of human CD4+ and CD8+ T cell responses against CMV proteins IE1 and IE2; Public Library of Science; Plos One; 9; 4; 4-2014; 1-12; e94892
1932-6203
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0094892
info:eu-repo/semantics/altIdentifier/doi/10.1371/journal.pone.0094892
info:eu-repo/semantics/altIdentifier/url/https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24760079/
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Public Library of Science
publisher.none.fl_str_mv Public Library of Science
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 13.070432

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