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dc.contributor.authorNunes-Alves, Claudio
dc.contributor.authorBooty, Matthew G.
dc.contributor.authorCarpenter, Stephen
dc.contributor.authorRothchild, Alissa C.
dc.contributor.authorMartin, Constance J.
dc.contributor.authorDesjardins, Danielle
dc.contributor.authorSteblenko, Katherine
dc.contributor.authorKloverpris, Henrik
dc.contributor.authorMadansein, Rajhmun
dc.contributor.authorRamsuran, Duran
dc.contributor.authorLeslie, Alasdair
dc.contributor.authorCorreia-Neves, Margarida
dc.contributor.authorBehar, Samuel M.
dc.date2022-08-11T08:09:18.000
dc.date.accessioned2022-08-23T16:25:53Z
dc.date.available2022-08-23T16:25:53Z
dc.date.issued2015-04-07
dc.date.submitted2015-04-03
dc.identifier.doi10.13028/M2WC7N
dc.identifier.urihttp://hdl.handle.net/20.500.14038/36442
dc.description<p>Data collection dates: 2014-2015. See Additional File that contains an explanation of the data fields in the spreadsheet.</p>
dc.description<p>Methodology is documented in published manuscript.</p>
dc.description.abstractManuscript abstract: 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 TCRβ bias. Using a retrogenic model of TB10.44-11-specific CD8+ T cells, 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-γ 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.
dc.description.sponsorshipNational Institute of Allergy and Infectious Diseases, National Institutes of Health, U.S. Department of Health and Human Services
dc.description.sponsorshipR01 AI106725
dc.format.medium.xlsx (14MB)
dc.language.isoen_US
dc.publishereScholarship@UMMS
dc.relation<p>This dataset (.xslx file, 14 MB) is the primary data source for the following published study: Nunes-Alves C, Booty MG, Carpenter SM, Rothchild AC, Martin CJ, Desjardins D, Steblenko K, Kløverpris HN, Madansein R, Ramsuran D, Leslie A, Correia-Neves M, Behar SM. <a href="http://escholarship.umassmed.edu/maps_pubs/13/" target="_blank" title="Human and Murine Clonal CD8+ T Cell Expansions Arise during Tuberculosis Because of TCR Selection">Human and Murine Clonal CD8+ T Cell Expansions Arise during Tuberculosis Because of TCR Selection</a>. PLoS Pathog. 2015 May 6;11(5):e1004849. doi: 10.1371/journal.ppat.1004849. eCollection 2015 May. PubMed PMID: 25945999; PubMed Central PMCID: PMC4422591.</p>
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.subjectMycobacterium tuberculosis
dc.subjectTuberculosis
dc.subjectTuberculosis vaccines
dc.subjectCD8+ T cells
dc.subjectT cell receptors
dc.subjectimmunodominance
dc.subjectImmunity
dc.subjectImmunology of Infectious Disease
dc.subjectImmunopathology
dc.subjectMicrobiology
dc.subjectPathogenic Microbiology
dc.titleData from: Human and Murine Clonal CD8+ T Cell Expansions Arise during Tuberculosis Because of TCR Selection
dc.typeDataset
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/maps_data/1
dc.identifier.contextkey6940742
dc.file.descriptionCode list information for dataset
refterms.dateFOA2022-08-31T01:42:26Z
html.description.abstract<p>Manuscript abstract: The immune system can recognize virtually any antigen, yet T cell responses against several pathogens, including <em>Mycobacterium tuberculosis</em>, 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 <em>M. tuberculosis </em>is dominated by TB10.44-11-specific T cells with extreme TCRβ bias. Using a retrogenic model of TB10.44-11-specific CD8+ T cells, 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-γ 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.</p>
dc.identifier.submissionpathmaps_data/1
dc.contributor.departmentDepartment of Microbiology and Physiological Systems


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