CD4 T Cell Responses to Theileria parva in Immune Cattle Recognize a Diverse Set of Parasite Antigens Presented on the Surface of Infected Lymphoblasts

Autores
Morrison, W. Ivan; Aguado, Adriana; Sheldrake, Tara A.; Palmateer, Nicholas C.; Ifeonu, Olukemi O.; Tretina, Kyle; Parsons, Keith; Fenoy, Luis Emilio; Connelley, Timothy; Nielsen, Morten; Silva, Joana C.
Año de publicación
2021
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Parasite-specific CD8 T cell responses play a key role in mediating immunity against Theileria parva in cattle (Bos taurus), and there is evidence that efficient induction of these responses requires CD4 T cell responses. However, information on the antigenic specificity of the CD4 T cell response is lacking. The current study used a high-throughput system for Ag identification using CD4 T cells from immune animals to screen a library of ~40,000 synthetic peptides representing 499 T. parva gene products. Use of CD4 T cells from 12 immune cattle, representing 12 MHC class II types, identified 26 Ags. Unlike CD8 T cell responses, which are focused on a few dominant Ags, multiple Ags were recognized by CD4 T cell responses of individual animals. The Ags had diverse properties, but included proteins encoded by two multimember gene families: five haloacid dehalogenases and five subtelomere-encoded variable secreted proteins. Most Ags had predicted signal peptides and/or were encoded by abundantly transcribed genes, but neither parameter on their own was reliable for predicting antigenicity. Mapping of the epitopes confirmed presentation by DR or DQ class II alleles and comparison of available T. parva genome sequences demonstrated that they included both conserved and polymorphic epitopes. Immunization of animals with vaccine vectors expressing two of the Ags demonstrated induction of CD4 T cell responses capable of recognizing parasitized cells. The results of this study provide detailed insight into the CD4 T cell responses induced by T. parva and identify Ags suitable for use in vaccine development.
Fil: Morrison, W. Ivan. University of Edinburgh; Reino Unido
Fil: Aguado, Adriana. University of Edinburgh; Reino Unido
Fil: Sheldrake, Tara A.. University of Edinburgh; Reino Unido
Fil: Palmateer, Nicholas C.. University of Maryland; Estados Unidos
Fil: Ifeonu, Olukemi O.. University of Maryland; Estados Unidos
Fil: Tretina, Kyle. University of Maryland; Estados Unidos
Fil: Parsons, Keith. Institute For Animal Health; Reino Unido
Fil: Fenoy, Luis Emilio. 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: Connelley, Timothy. University of Edinburgh; Reino Unido
Fil: Nielsen, Morten. 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. Technical University of Denmark; Dinamarca
Fil: Silva, Joana C.. University of Maryland; Estados Unidos
Materia
CD4+ RESPONSE
THEILERIA PARVA
ANTIGEN IDENTIFICATION
VACCINE DEVELOPMENT
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/182967
Acceder
id CONICETDig_5d4733a108cdfc92d8a2bc172e889278
oai_identifier_str oai:ri.conicet.gov.ar:11336/182967
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling CD4 T Cell Responses to Theileria parva in Immune Cattle Recognize a Diverse Set of Parasite Antigens Presented on the Surface of Infected LymphoblastsMorrison, W. IvanAguado, AdrianaSheldrake, Tara A.Palmateer, Nicholas C.Ifeonu, Olukemi O.Tretina, KyleParsons, KeithFenoy, Luis EmilioConnelley, TimothyNielsen, MortenSilva, Joana C.CD4+ RESPONSETHEILERIA PARVAANTIGEN IDENTIFICATIONVACCINE DEVELOPMENThttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Parasite-specific CD8 T cell responses play a key role in mediating immunity against Theileria parva in cattle (Bos taurus), and there is evidence that efficient induction of these responses requires CD4 T cell responses. However, information on the antigenic specificity of the CD4 T cell response is lacking. The current study used a high-throughput system for Ag identification using CD4 T cells from immune animals to screen a library of ~40,000 synthetic peptides representing 499 T. parva gene products. Use of CD4 T cells from 12 immune cattle, representing 12 MHC class II types, identified 26 Ags. Unlike CD8 T cell responses, which are focused on a few dominant Ags, multiple Ags were recognized by CD4 T cell responses of individual animals. The Ags had diverse properties, but included proteins encoded by two multimember gene families: five haloacid dehalogenases and five subtelomere-encoded variable secreted proteins. Most Ags had predicted signal peptides and/or were encoded by abundantly transcribed genes, but neither parameter on their own was reliable for predicting antigenicity. Mapping of the epitopes confirmed presentation by DR or DQ class II alleles and comparison of available T. parva genome sequences demonstrated that they included both conserved and polymorphic epitopes. Immunization of animals with vaccine vectors expressing two of the Ags demonstrated induction of CD4 T cell responses capable of recognizing parasitized cells. The results of this study provide detailed insight into the CD4 T cell responses induced by T. parva and identify Ags suitable for use in vaccine development.Fil: Morrison, W. Ivan. University of Edinburgh; Reino UnidoFil: Aguado, Adriana. University of Edinburgh; Reino UnidoFil: Sheldrake, Tara A.. University of Edinburgh; Reino UnidoFil: Palmateer, Nicholas C.. University of Maryland; Estados UnidosFil: Ifeonu, Olukemi O.. University of Maryland; Estados UnidosFil: Tretina, Kyle. University of Maryland; Estados UnidosFil: Parsons, Keith. Institute For Animal Health; Reino UnidoFil: Fenoy, Luis Emilio. 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: Connelley, Timothy. University of Edinburgh; Reino UnidoFil: Nielsen, Morten. 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. Technical University of Denmark; DinamarcaFil: Silva, Joana C.. University of Maryland; Estados UnidosAmerican Association of Immunologists2021-09info: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/11336/182967Morrison, W. Ivan; Aguado, Adriana; Sheldrake, Tara A.; Palmateer, Nicholas C.; Ifeonu, Olukemi O.; et al.; CD4 T Cell Responses to Theileria parva in Immune Cattle Recognize a Diverse Set of Parasite Antigens Presented on the Surface of Infected Lymphoblasts; American Association of Immunologists; Journal of Immunology; 207; 8; 9-2021; 1965-19770022-1767CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/http://www.jimmunol.org/lookup/doi/10.4049/jimmunol.2100331info:eu-repo/semantics/altIdentifier/doi/10.4049/jimmunol.2100331info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-22T11:45:12Zoai:ri.conicet.gov.ar:11336/182967instacron: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:34982025-10-22 11:45:13.043CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv CD4 T Cell Responses to Theileria parva in Immune Cattle Recognize a Diverse Set of Parasite Antigens Presented on the Surface of Infected Lymphoblasts
title CD4 T Cell Responses to Theileria parva in Immune Cattle Recognize a Diverse Set of Parasite Antigens Presented on the Surface of Infected Lymphoblasts
spellingShingle CD4 T Cell Responses to Theileria parva in Immune Cattle Recognize a Diverse Set of Parasite Antigens Presented on the Surface of Infected Lymphoblasts
Morrison, W. Ivan
CD4+ RESPONSE
THEILERIA PARVA
ANTIGEN IDENTIFICATION
VACCINE DEVELOPMENT
title_short CD4 T Cell Responses to Theileria parva in Immune Cattle Recognize a Diverse Set of Parasite Antigens Presented on the Surface of Infected Lymphoblasts
title_full CD4 T Cell Responses to Theileria parva in Immune Cattle Recognize a Diverse Set of Parasite Antigens Presented on the Surface of Infected Lymphoblasts
title_fullStr CD4 T Cell Responses to Theileria parva in Immune Cattle Recognize a Diverse Set of Parasite Antigens Presented on the Surface of Infected Lymphoblasts
title_full_unstemmed CD4 T Cell Responses to Theileria parva in Immune Cattle Recognize a Diverse Set of Parasite Antigens Presented on the Surface of Infected Lymphoblasts
title_sort CD4 T Cell Responses to Theileria parva in Immune Cattle Recognize a Diverse Set of Parasite Antigens Presented on the Surface of Infected Lymphoblasts
dc.creator.none.fl_str_mv Morrison, W. Ivan
Aguado, Adriana
Sheldrake, Tara A.
Palmateer, Nicholas C.
Ifeonu, Olukemi O.
Tretina, Kyle
Parsons, Keith
Fenoy, Luis Emilio
Connelley, Timothy
Nielsen, Morten
Silva, Joana C.
author Morrison, W. Ivan
author_facet Morrison, W. Ivan
Aguado, Adriana
Sheldrake, Tara A.
Palmateer, Nicholas C.
Ifeonu, Olukemi O.
Tretina, Kyle
Parsons, Keith
Fenoy, Luis Emilio
Connelley, Timothy
Nielsen, Morten
Silva, Joana C.
author_role author
author2 Aguado, Adriana
Sheldrake, Tara A.
Palmateer, Nicholas C.
Ifeonu, Olukemi O.
Tretina, Kyle
Parsons, Keith
Fenoy, Luis Emilio
Connelley, Timothy
Nielsen, Morten
Silva, Joana C.
author2_role author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv CD4+ RESPONSE
THEILERIA PARVA
ANTIGEN IDENTIFICATION
VACCINE DEVELOPMENT
topic CD4+ RESPONSE
THEILERIA PARVA
ANTIGEN IDENTIFICATION
VACCINE DEVELOPMENT
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Parasite-specific CD8 T cell responses play a key role in mediating immunity against Theileria parva in cattle (Bos taurus), and there is evidence that efficient induction of these responses requires CD4 T cell responses. However, information on the antigenic specificity of the CD4 T cell response is lacking. The current study used a high-throughput system for Ag identification using CD4 T cells from immune animals to screen a library of ~40,000 synthetic peptides representing 499 T. parva gene products. Use of CD4 T cells from 12 immune cattle, representing 12 MHC class II types, identified 26 Ags. Unlike CD8 T cell responses, which are focused on a few dominant Ags, multiple Ags were recognized by CD4 T cell responses of individual animals. The Ags had diverse properties, but included proteins encoded by two multimember gene families: five haloacid dehalogenases and five subtelomere-encoded variable secreted proteins. Most Ags had predicted signal peptides and/or were encoded by abundantly transcribed genes, but neither parameter on their own was reliable for predicting antigenicity. Mapping of the epitopes confirmed presentation by DR or DQ class II alleles and comparison of available T. parva genome sequences demonstrated that they included both conserved and polymorphic epitopes. Immunization of animals with vaccine vectors expressing two of the Ags demonstrated induction of CD4 T cell responses capable of recognizing parasitized cells. The results of this study provide detailed insight into the CD4 T cell responses induced by T. parva and identify Ags suitable for use in vaccine development.
Fil: Morrison, W. Ivan. University of Edinburgh; Reino Unido
Fil: Aguado, Adriana. University of Edinburgh; Reino Unido
Fil: Sheldrake, Tara A.. University of Edinburgh; Reino Unido
Fil: Palmateer, Nicholas C.. University of Maryland; Estados Unidos
Fil: Ifeonu, Olukemi O.. University of Maryland; Estados Unidos
Fil: Tretina, Kyle. University of Maryland; Estados Unidos
Fil: Parsons, Keith. Institute For Animal Health; Reino Unido
Fil: Fenoy, Luis Emilio. 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: Connelley, Timothy. University of Edinburgh; Reino Unido
Fil: Nielsen, Morten. 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. Technical University of Denmark; Dinamarca
Fil: Silva, Joana C.. University of Maryland; Estados Unidos
description Parasite-specific CD8 T cell responses play a key role in mediating immunity against Theileria parva in cattle (Bos taurus), and there is evidence that efficient induction of these responses requires CD4 T cell responses. However, information on the antigenic specificity of the CD4 T cell response is lacking. The current study used a high-throughput system for Ag identification using CD4 T cells from immune animals to screen a library of ~40,000 synthetic peptides representing 499 T. parva gene products. Use of CD4 T cells from 12 immune cattle, representing 12 MHC class II types, identified 26 Ags. Unlike CD8 T cell responses, which are focused on a few dominant Ags, multiple Ags were recognized by CD4 T cell responses of individual animals. The Ags had diverse properties, but included proteins encoded by two multimember gene families: five haloacid dehalogenases and five subtelomere-encoded variable secreted proteins. Most Ags had predicted signal peptides and/or were encoded by abundantly transcribed genes, but neither parameter on their own was reliable for predicting antigenicity. Mapping of the epitopes confirmed presentation by DR or DQ class II alleles and comparison of available T. parva genome sequences demonstrated that they included both conserved and polymorphic epitopes. Immunization of animals with vaccine vectors expressing two of the Ags demonstrated induction of CD4 T cell responses capable of recognizing parasitized cells. The results of this study provide detailed insight into the CD4 T cell responses induced by T. parva and identify Ags suitable for use in vaccine development.
publishDate 2021
dc.date.none.fl_str_mv 2021-09
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/11336/182967
Morrison, W. Ivan; Aguado, Adriana; Sheldrake, Tara A.; Palmateer, Nicholas C.; Ifeonu, Olukemi O.; et al.; CD4 T Cell Responses to Theileria parva in Immune Cattle Recognize a Diverse Set of Parasite Antigens Presented on the Surface of Infected Lymphoblasts; American Association of Immunologists; Journal of Immunology; 207; 8; 9-2021; 1965-1977
0022-1767
CONICET Digital
CONICET
url http://hdl.handle.net/11336/182967
identifier_str_mv Morrison, W. Ivan; Aguado, Adriana; Sheldrake, Tara A.; Palmateer, Nicholas C.; Ifeonu, Olukemi O.; et al.; CD4 T Cell Responses to Theileria parva in Immune Cattle Recognize a Diverse Set of Parasite Antigens Presented on the Surface of Infected Lymphoblasts; American Association of Immunologists; Journal of Immunology; 207; 8; 9-2021; 1965-1977
0022-1767
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/http://www.jimmunol.org/lookup/doi/10.4049/jimmunol.2100331
info:eu-repo/semantics/altIdentifier/doi/10.4049/jimmunol.2100331
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv American Association of Immunologists
publisher.none.fl_str_mv American Association of Immunologists
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 12.982451

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