Need for tripeptidyl-peptidase II in major histocompatibility complex class I viral antigen processing when proteasomes are detrimental

CD8(+) T lymphocytes recognize infected cells that display virus-derived antigenic peptides complexed with major histocompatibility complex class I molecules. Peptides are mainly byproducts of cellular protein turnover by cytosolic proteasomes. Cytosolic tripeptidyl-peptidase II (TPPII) also partici...

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Authors: Guil, Sara, Rodríguez-Castro, Marta, Aguilar, Francisco, Villasevil, Eugenia M, Antón, Luis C, Val, Margarita del
Format: article
Publication Date:2006
Country:España
Institution:Instituto de Salud Carlos III (ISCIII)
Repository:Repisalud
Language:English
OAI Identifier:oai:repisalud.isciii.es:20.500.12105/9695
Online Access:http://hdl.handle.net/20.500.12105/9695
Access Level:Open access
Keyword:Acetylcysteine
Amino Acid Sequence
Aminopeptidases
Animals
Antigen Presentation
Antigens, Viral
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spelling Need for tripeptidyl-peptidase II in major histocompatibility complex class I viral antigen processing when proteasomes are detrimentalGuil, SaraRodríguez-Castro, MartaAguilar, FranciscoVillasevil, Eugenia MAntón, Luis CVal, Margarita delAcetylcysteineAmino Acid SequenceAminopeptidasesAnimalsAntigen PresentationAntigens, ViralCD8(+) T lymphocytes recognize infected cells that display virus-derived antigenic peptides complexed with major histocompatibility complex class I molecules. Peptides are mainly byproducts of cellular protein turnover by cytosolic proteasomes. Cytosolic tripeptidyl-peptidase II (TPPII) also participates in protein degradation. Several peptidic epitopes unexpectedly do not require proteasomes, but it is unclear which proteases generate them. We studied antigen processing of influenza virus nucleoprotein epitope NP(147-155), an archetype epitope that is even destroyed by a proteasome-mediated mechanism. TPPII, with the assistance of endoplasmic reticulum trimming metallo-aminopeptidases, probably ERAAP (endoplasmic reticulum aminopeptidase associated with antigen processing), was crucial for nucleoprotein epitope generation both in the presence of functional proteasomes and when blocked by lactacystin, as shown with specific chemical inhibitors and gene silencing. Different protein contexts and subcellular targeting all allowed epitope processing by TPPII as well as trimming. The results show the plasticity of the cell's assortment of proteases for providing ligands for recognition by antiviral CD8(+) T cells. Our observations identify for the first time a set of proteases competent for antigen processing of an epitope that is susceptible to destruction by proteasomes.American Society for Biochemistry and Molecular Biology (ASBMB)Ministerio de Educación y Ciencia (España)Instituto de Salud Carlos IIIFundación Ramón ArecesComunidad de Madrid (España)20202020-04-2320062006-12-2920062006-12-29research articlehttp://purl.org/coar/resource_type/c_2df8fbb1VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/20.500.12105/9695reponame:Repisaludinstname:Instituto de Salud Carlos III (ISCIII)Inglésengopen accesshttp://purl.org/coar/access_right/c_abf2Atribución-NoComercial-CompartirIgual 4.0 Internacionalhttp://creativecommons.org/licenses/by-nc-sa/4.0/info:eu-repo/semantics/openAccessoai:repisalud.isciii.es:20.500.12105/96952026-06-12T12:43:37Z
dc.title.none.fl_str_mv Need for tripeptidyl-peptidase II in major histocompatibility complex class I viral antigen processing when proteasomes are detrimental
title Need for tripeptidyl-peptidase II in major histocompatibility complex class I viral antigen processing when proteasomes are detrimental
spellingShingle Need for tripeptidyl-peptidase II in major histocompatibility complex class I viral antigen processing when proteasomes are detrimental
Guil, Sara
Acetylcysteine
Amino Acid Sequence
Aminopeptidases
Animals
Antigen Presentation
Antigens, Viral
title_short Need for tripeptidyl-peptidase II in major histocompatibility complex class I viral antigen processing when proteasomes are detrimental
title_full Need for tripeptidyl-peptidase II in major histocompatibility complex class I viral antigen processing when proteasomes are detrimental
title_fullStr Need for tripeptidyl-peptidase II in major histocompatibility complex class I viral antigen processing when proteasomes are detrimental
title_full_unstemmed Need for tripeptidyl-peptidase II in major histocompatibility complex class I viral antigen processing when proteasomes are detrimental
title_sort Need for tripeptidyl-peptidase II in major histocompatibility complex class I viral antigen processing when proteasomes are detrimental
dc.creator.none.fl_str_mv Guil, Sara
Rodríguez-Castro, Marta
Aguilar, Francisco
Villasevil, Eugenia M
Antón, Luis C
Val, Margarita del
author Guil, Sara
author_facet Guil, Sara
Rodríguez-Castro, Marta
Aguilar, Francisco
Villasevil, Eugenia M
Antón, Luis C
Val, Margarita del
author_role author
author2 Rodríguez-Castro, Marta
Aguilar, Francisco
Villasevil, Eugenia M
Antón, Luis C
Val, Margarita del
author2_role author
author
author
author
author
dc.contributor.none.fl_str_mv Ministerio de Educación y Ciencia (España)
Instituto de Salud Carlos III
Fundación Ramón Areces
Comunidad de Madrid (España)
dc.subject.none.fl_str_mv Acetylcysteine
Amino Acid Sequence
Aminopeptidases
Animals
Antigen Presentation
Antigens, Viral
topic Acetylcysteine
Amino Acid Sequence
Aminopeptidases
Animals
Antigen Presentation
Antigens, Viral
description CD8(+) T lymphocytes recognize infected cells that display virus-derived antigenic peptides complexed with major histocompatibility complex class I molecules. Peptides are mainly byproducts of cellular protein turnover by cytosolic proteasomes. Cytosolic tripeptidyl-peptidase II (TPPII) also participates in protein degradation. Several peptidic epitopes unexpectedly do not require proteasomes, but it is unclear which proteases generate them. We studied antigen processing of influenza virus nucleoprotein epitope NP(147-155), an archetype epitope that is even destroyed by a proteasome-mediated mechanism. TPPII, with the assistance of endoplasmic reticulum trimming metallo-aminopeptidases, probably ERAAP (endoplasmic reticulum aminopeptidase associated with antigen processing), was crucial for nucleoprotein epitope generation both in the presence of functional proteasomes and when blocked by lactacystin, as shown with specific chemical inhibitors and gene silencing. Different protein contexts and subcellular targeting all allowed epitope processing by TPPII as well as trimming. The results show the plasticity of the cell's assortment of proteases for providing ligands for recognition by antiviral CD8(+) T cells. Our observations identify for the first time a set of proteases competent for antigen processing of an epitope that is susceptible to destruction by proteasomes.
publishDate 2006
dc.date.none.fl_str_mv 2006
2006-12-29
2006
2006-12-29
2020
2020-04-23
dc.type.none.fl_str_mv research article
http://purl.org/coar/resource_type/c_2df8fbb1
VoR
http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv http://hdl.handle.net/20.500.12105/9695
url http://hdl.handle.net/20.500.12105/9695
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
Atribución-NoComercial-CompartirIgual 4.0 Internacional
http://creativecommons.org/licenses/by-nc-sa/4.0/
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
Atribución-NoComercial-CompartirIgual 4.0 Internacional
http://creativecommons.org/licenses/by-nc-sa/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv American Society for Biochemistry and Molecular Biology (ASBMB)
publisher.none.fl_str_mv American Society for Biochemistry and Molecular Biology (ASBMB)
dc.source.none.fl_str_mv reponame:Repisalud
instname:Instituto de Salud Carlos III (ISCIII)
instname_str Instituto de Salud Carlos III (ISCIII)
reponame_str Repisalud
collection Repisalud
repository.name.fl_str_mv
repository.mail.fl_str_mv
_version_ 1869411924524924928
score 15,811543

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