A higher activation threshold of memory CD8+ T cells has a fitness cost that is modified by TCR affinity during Tuberculosis

Detalhes bibliográficos
Autor(a) principal: Carpenter, Stephen M
Data de Publicação: 2016
Outros Autores: Nunes-Alves, Cláudio, Booty, Matthew G, Way, Sing Sing, Behar, Samuel M
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: http://hdl.handle.net/1822/58118
Resumo: All relevant data are within the paper and its Supporting Information files except for the primary TCR sequences. The data files for the primary TCR sequences are publicly deposited in the University of Massachusetts Medical School’s institutional repository, eScholarship@UMMS. The permanent link to the data is http://dx.doi.org/10.13028/M2CC70
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spelling A higher activation threshold of memory CD8+ T cells has a fitness cost that is modified by TCR affinity during TuberculosisAdoptive TransferAnimalsCD8-Positive T-LymphocytesCell SeparationDisease Models, AnimalEnzyme-Linked Immunosorbent AssayFlow CytometryHigh-Throughput Nucleotide SequencingImmunologic MemoryLymphocyte ActivationMiceMice, Inbred C57BLMice, KnockoutMice, TransgenicReceptors, Antigen, T-CellTuberculosisTuberculosis VaccinesScience & TechnologyAll relevant data are within the paper and its Supporting Information files except for the primary TCR sequences. The data files for the primary TCR sequences are publicly deposited in the University of Massachusetts Medical School’s institutional repository, eScholarship@UMMS. The permanent link to the data is http://dx.doi.org/10.13028/M2CC70T cell vaccines against Mycobacterium tuberculosis (Mtb) and other pathogens are based on the principle that memory T cells rapidly generate effector responses upon challenge, leading to pathogen clearance. Despite eliciting a robust memory CD8+ T cell response to the immunodominant Mtb antigen TB10.4 (EsxH), we find the increased frequency of TB10.4-specific CD8+ T cells conferred by vaccination to be short-lived after Mtb challenge. To compare memory and naïve CD8+ T cell function during their response to Mtb, we track their expansions using TB10.4-specific retrogenic CD8+ T cells. We find that the primary (naïve) response outnumbers the secondary (memory) response during Mtb challenge, an effect moderated by increased TCR affinity. To determine whether the expansion of polyclonal memory T cells is restrained following Mtb challenge, we used TCRβ deep sequencing to track TB10.4-specific CD8+ T cells after vaccination and subsequent challenge in intact mice. Successful memory T cells, defined by their clonal expansion after Mtb challenge, express similar CDR3β sequences suggesting TCR selection by antigen. Thus, both TCR-dependent and -independent factors affect the fitness of memory CD8+ responses. The impaired expansion of the majority of memory T cell clonotypes may explain why some TB vaccines have not provided better protection.This work was supported by NIH R01 AI106725 as well as fellowship funding to SC from NIH AI T32 007061 and the UMass GSBS Millennium Program. The Small Animal Biocontainment Suite was supported in part by Center for AIDS Research Grant P30 AI 060354. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.info:eu-repo/semantics/publishedVersionPublic Library of ScienceUniversidade do MinhoCarpenter, Stephen MNunes-Alves, CláudioBooty, Matthew GWay, Sing SingBehar, Samuel M2016-012016-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/1822/58118engCarpenter SM, Nunes-Alves C, Booty MG, Way SS, Behar SM (2016) A higher activation threshold of memory CD8+ T cells has a fitness cost that is modified by TCR affinity during Tuberculosis. PLoSPathog12(1):e1005380. doi:10.1371/journal.ppat.10053801553-736610.1371/journal.ppat.100538026745507https://journals.plos.org/plospathogens/article/file?id=10.1371/journal.ppat.1005380info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2024-05-11T07:13:30Zoai:repositorium.sdum.uminho.pt:1822/58118Portal AgregadorONGhttps://www.rcaap.pt/oai/openairemluisa.alvim@gmail.comopendoar:71602024-05-11T07:13:30Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse
dc.title.none.fl_str_mv A higher activation threshold of memory CD8+ T cells has a fitness cost that is modified by TCR affinity during Tuberculosis
title A higher activation threshold of memory CD8+ T cells has a fitness cost that is modified by TCR affinity during Tuberculosis
spellingShingle A higher activation threshold of memory CD8+ T cells has a fitness cost that is modified by TCR affinity during Tuberculosis
Carpenter, Stephen M
Adoptive Transfer
Animals
CD8-Positive T-Lymphocytes
Cell Separation
Disease Models, Animal
Enzyme-Linked Immunosorbent Assay
Flow Cytometry
High-Throughput Nucleotide Sequencing
Immunologic Memory
Lymphocyte Activation
Mice
Mice, Inbred C57BL
Mice, Knockout
Mice, Transgenic
Receptors, Antigen, T-Cell
Tuberculosis
Tuberculosis Vaccines
Science & Technology
title_short A higher activation threshold of memory CD8+ T cells has a fitness cost that is modified by TCR affinity during Tuberculosis
title_full A higher activation threshold of memory CD8+ T cells has a fitness cost that is modified by TCR affinity during Tuberculosis
title_fullStr A higher activation threshold of memory CD8+ T cells has a fitness cost that is modified by TCR affinity during Tuberculosis
title_full_unstemmed A higher activation threshold of memory CD8+ T cells has a fitness cost that is modified by TCR affinity during Tuberculosis
title_sort A higher activation threshold of memory CD8+ T cells has a fitness cost that is modified by TCR affinity during Tuberculosis
author Carpenter, Stephen M
author_facet Carpenter, Stephen M
Nunes-Alves, Cláudio
Booty, Matthew G
Way, Sing Sing
Behar, Samuel M
author_role author
author2 Nunes-Alves, Cláudio
Booty, Matthew G
Way, Sing Sing
Behar, Samuel M
author2_role author
author
author
author
dc.contributor.none.fl_str_mv Universidade do Minho
dc.contributor.author.fl_str_mv Carpenter, Stephen M
Nunes-Alves, Cláudio
Booty, Matthew G
Way, Sing Sing
Behar, Samuel M
dc.subject.por.fl_str_mv Adoptive Transfer
Animals
CD8-Positive T-Lymphocytes
Cell Separation
Disease Models, Animal
Enzyme-Linked Immunosorbent Assay
Flow Cytometry
High-Throughput Nucleotide Sequencing
Immunologic Memory
Lymphocyte Activation
Mice
Mice, Inbred C57BL
Mice, Knockout
Mice, Transgenic
Receptors, Antigen, T-Cell
Tuberculosis
Tuberculosis Vaccines
Science & Technology
topic Adoptive Transfer
Animals
CD8-Positive T-Lymphocytes
Cell Separation
Disease Models, Animal
Enzyme-Linked Immunosorbent Assay
Flow Cytometry
High-Throughput Nucleotide Sequencing
Immunologic Memory
Lymphocyte Activation
Mice
Mice, Inbred C57BL
Mice, Knockout
Mice, Transgenic
Receptors, Antigen, T-Cell
Tuberculosis
Tuberculosis Vaccines
Science & Technology
description All relevant data are within the paper and its Supporting Information files except for the primary TCR sequences. The data files for the primary TCR sequences are publicly deposited in the University of Massachusetts Medical School’s institutional repository, eScholarship@UMMS. The permanent link to the data is http://dx.doi.org/10.13028/M2CC70
publishDate 2016
dc.date.none.fl_str_mv 2016-01
2016-01-01T00:00:00Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://hdl.handle.net/1822/58118
url http://hdl.handle.net/1822/58118
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv Carpenter SM, Nunes-Alves C, Booty MG, Way SS, Behar SM (2016) A higher activation threshold of memory CD8+ T cells has a fitness cost that is modified by TCR affinity during Tuberculosis. PLoSPathog12(1):e1005380. doi:10.1371/journal.ppat.1005380
1553-7366
10.1371/journal.ppat.1005380
26745507
https://journals.plos.org/plospathogens/article/file?id=10.1371/journal.ppat.1005380
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv 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:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron:RCAAP
instname_str Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron_str RCAAP
institution RCAAP
reponame_str Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
collection Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
repository.name.fl_str_mv Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
repository.mail.fl_str_mv mluisa.alvim@gmail.com
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