Human and murine clonal CD8+ T cell expansions arise during tuberculosis because of TCR selection
Autor(a) principal: | |
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Data de Publicação: | 2015 |
Outros Autores: | , , , , , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | http://hdl.handle.net/1822/40054 |
Resumo: | The immune system can recognize virtually any antigen, yet T cell responses against several pathogens, including Mycobacterium tuberculosis, are restricted to a limited number of immunodominant epitopes. The host factors that affect immunodominance are incompletely understood. Whether immunodominant epitopes elicit protective CD8+ T cell responses or instead act as decoys to subvert immunity and allow pathogens to establish chronic infection is unknown. Here we show that anatomically distinct human granulomas contain clonally expanded CD8+ T cells with overlapping T cell receptor (TCR) repertoires. Similarly, the murine CD8+ T cell response against M. tuberculosis is dominated by TB10.44-11-specific T cells with extreme TCRß bias. Using a retro genic model of TB10.44-11-specific CD8+ Tcells, we show that TCR dominance can arise because of competition between clonotypes driven by differences in affinity. Finally, we demonstrate that TB10.4-specific CD8+ T cells mediate protection against tuberculosis, which requires interferon-? production and TAP1-dependent antigen presentation in vivo. Our study of how immunodominance, biased TCR repertoires, and protection are inter-related, provides a new way to measure the quality of T cell immunity, which if applied to vaccine evaluation, could enhance our understanding of how to elicit protective T cell immunity. |
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Human and murine clonal CD8+ T cell expansions arise during tuberculosis because of TCR selectionScience & TechnologyThe immune system can recognize virtually any antigen, yet T cell responses against several pathogens, including Mycobacterium tuberculosis, are restricted to a limited number of immunodominant epitopes. The host factors that affect immunodominance are incompletely understood. Whether immunodominant epitopes elicit protective CD8+ T cell responses or instead act as decoys to subvert immunity and allow pathogens to establish chronic infection is unknown. Here we show that anatomically distinct human granulomas contain clonally expanded CD8+ T cells with overlapping T cell receptor (TCR) repertoires. Similarly, the murine CD8+ T cell response against M. tuberculosis is dominated by TB10.44-11-specific T cells with extreme TCRß bias. Using a retro genic model of TB10.44-11-specific CD8+ Tcells, we show that TCR dominance can arise because of competition between clonotypes driven by differences in affinity. Finally, we demonstrate that TB10.4-specific CD8+ T cells mediate protection against tuberculosis, which requires interferon-? production and TAP1-dependent antigen presentation in vivo. Our study of how immunodominance, biased TCR repertoires, and protection are inter-related, provides a new way to measure the quality of T cell immunity, which if applied to vaccine evaluation, could enhance our understanding of how to elicit protective T cell immunity.This work was supported by the Portuguese Foundation for Science and Technology individual fellowship (CNA) www.fct.pt, a National Institutes of Health Grant R01 AI106725 (SMB) www.nih.gov, and a Center for AIDS Research Grant P30 AI 060354 (SMB) www.nih.gov. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Public Library of Science (PLOS)Universidade do MinhoAlves, Cláudio NunesBooty, Matthew G.Carpenter, Stephen M.Rothchild, Alissa C.Martin, Constance J.Desjardins, DanielleSteblenko, KatherineKløverpris, Henrik N.Madansein, RajhmunRamsuran, DuranLeslie, AlasdairNeves, Margarida CorreiaBehar, Samuel M.20152015-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/1822/40054engNunes-Alves, C., Booty, M. G., Carpenter, S. M., Rothchild, A. C., Martin, C. J., Desjardins, D., . . . Behar, S. M. (2015). Human and Murine Clonal CD8+T Cell Expansions Arise during Tuberculosis Because of TCR Selection. PLoS Pathogens, 11(5). doi: 10.1371/journal.ppat.10048491553-736610.1371/journal.ppat.100484925945999http://journals.plos.org/plospathogens/info: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:RCAAP2023-07-21T12:22:04Zoai:repositorium.sdum.uminho.pt:1822/40054Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T19:15:31.329686Repositório 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 |
Human and murine clonal CD8+ T cell expansions arise during tuberculosis because of TCR selection |
title |
Human and murine clonal CD8+ T cell expansions arise during tuberculosis because of TCR selection |
spellingShingle |
Human and murine clonal CD8+ T cell expansions arise during tuberculosis because of TCR selection Alves, Cláudio Nunes Science & Technology |
title_short |
Human and murine clonal CD8+ T cell expansions arise during tuberculosis because of TCR selection |
title_full |
Human and murine clonal CD8+ T cell expansions arise during tuberculosis because of TCR selection |
title_fullStr |
Human and murine clonal CD8+ T cell expansions arise during tuberculosis because of TCR selection |
title_full_unstemmed |
Human and murine clonal CD8+ T cell expansions arise during tuberculosis because of TCR selection |
title_sort |
Human and murine clonal CD8+ T cell expansions arise during tuberculosis because of TCR selection |
author |
Alves, Cláudio Nunes |
author_facet |
Alves, Cláudio Nunes Booty, Matthew G. Carpenter, Stephen M. Rothchild, Alissa C. Martin, Constance J. Desjardins, Danielle Steblenko, Katherine Kløverpris, Henrik N. Madansein, Rajhmun Ramsuran, Duran Leslie, Alasdair Neves, Margarida Correia Behar, Samuel M. |
author_role |
author |
author2 |
Booty, Matthew G. Carpenter, Stephen M. Rothchild, Alissa C. Martin, Constance J. Desjardins, Danielle Steblenko, Katherine Kløverpris, Henrik N. Madansein, Rajhmun Ramsuran, Duran Leslie, Alasdair Neves, Margarida Correia Behar, Samuel M. |
author2_role |
author author author author author author author author author author author author |
dc.contributor.none.fl_str_mv |
Universidade do Minho |
dc.contributor.author.fl_str_mv |
Alves, Cláudio Nunes Booty, Matthew G. Carpenter, Stephen M. Rothchild, Alissa C. Martin, Constance J. Desjardins, Danielle Steblenko, Katherine Kløverpris, Henrik N. Madansein, Rajhmun Ramsuran, Duran Leslie, Alasdair Neves, Margarida Correia Behar, Samuel M. |
dc.subject.por.fl_str_mv |
Science & Technology |
topic |
Science & Technology |
description |
The immune system can recognize virtually any antigen, yet T cell responses against several pathogens, including Mycobacterium tuberculosis, are restricted to a limited number of immunodominant epitopes. The host factors that affect immunodominance are incompletely understood. Whether immunodominant epitopes elicit protective CD8+ T cell responses or instead act as decoys to subvert immunity and allow pathogens to establish chronic infection is unknown. Here we show that anatomically distinct human granulomas contain clonally expanded CD8+ T cells with overlapping T cell receptor (TCR) repertoires. Similarly, the murine CD8+ T cell response against M. tuberculosis is dominated by TB10.44-11-specific T cells with extreme TCRß bias. Using a retro genic model of TB10.44-11-specific CD8+ Tcells, we show that TCR dominance can arise because of competition between clonotypes driven by differences in affinity. Finally, we demonstrate that TB10.4-specific CD8+ T cells mediate protection against tuberculosis, which requires interferon-? production and TAP1-dependent antigen presentation in vivo. Our study of how immunodominance, biased TCR repertoires, and protection are inter-related, provides a new way to measure the quality of T cell immunity, which if applied to vaccine evaluation, could enhance our understanding of how to elicit protective T cell immunity. |
publishDate |
2015 |
dc.date.none.fl_str_mv |
2015 2015-01-01T00:00:00Z |
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/1822/40054 |
url |
http://hdl.handle.net/1822/40054 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Nunes-Alves, C., Booty, M. G., Carpenter, S. M., Rothchild, A. C., Martin, C. J., Desjardins, D., . . . Behar, S. M. (2015). Human and Murine Clonal CD8+T Cell Expansions Arise during Tuberculosis Because of TCR Selection. PLoS Pathogens, 11(5). doi: 10.1371/journal.ppat.1004849 1553-7366 10.1371/journal.ppat.1004849 25945999 http://journals.plos.org/plospathogens/ |
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 (PLOS) |
publisher.none.fl_str_mv |
Public Library of Science (PLOS) |
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 |
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Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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RCAAP |
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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 |
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1799132601530712064 |