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dc.contributor.authorCarpenter, Stephen M.
dc.contributor.authorNunes-Alves, Claudio
dc.contributor.authorBooty, Matthew G.
dc.contributor.authorWay, Sing Sing
dc.contributor.authorBehar, Samuel M.
dc.date2022-08-11T08:09:18.000
dc.date.accessioned2022-08-23T16:25:54Z
dc.date.available2022-08-23T16:25:54Z
dc.date.issued2015-12-15
dc.date.submitted2015-12-15
dc.identifier.doi10.13028/M2CC70
dc.identifier.urihttp://hdl.handle.net/20.500.14038/36444
dc.description<p>See Additional File that contains an explanation of the data fields in the spreadsheet. Data collection dates: 2014-2015.</p>
dc.description<p>Methodology is documented in published manuscript.</p>
dc.description.abstractManuscript abstract: T 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.
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 (4 MB)
dc.language.isoen_US
dc.publishereScholarship@UMMS
dc.relation<p>This dataset is the primary data source for the following published study: Carpenter SM, Nunes-Alves C, Booty MG, Way SS, Behar SM. <a href="http://escholarship.umassmed.edu/maps_pubs/15/" target="_blank" title="A Higher Activation Threshold of Memory CD8+ T Cells Has a Fitness Cost That Is Modified by TCR Affinity during Tuberculosis">A Higher Activation Threshold of Memory CD8+ T Cells Has a Fitness Cost That Is Modified by TCR Affinity during Tuberculosis</a>. PLoS Pathog. 2016 Jan 8;12(1):e1005380. doi:10.1371/journal.ppat.1005380. eCollection 2016 Jan. PubMed PMID: 26745507; PubMed Central PMCID: PMC4706326.</p>
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.subjectT cells
dc.subjectCytotoxic T cells
dc.subjectMemory T cells
dc.subjectMycobacterium tuberculosis
dc.subjectVaccination and immunization
dc.subjectImmunity
dc.subjectImmunology of Infectious Disease
dc.subjectImmunopathology
dc.subjectImmunoprophylaxis and Therapy
dc.subjectPathogenic Microbiology
dc.titleData from: A Higher Activation Threshold of Memory CD8+ T Cells Has a Fitness Cost That Is Modified by TCR Affinity during Tuberculosis
dc.typeDataset
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/maps_data/3
dc.identifier.contextkey7948889
dc.file.descriptionCode list information for dataset
refterms.dateFOA2022-08-31T00:27:03Z
html.description.abstract<p>Manuscript abstract: T 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.</p>
dc.identifier.submissionpathmaps_data/3
dc.contributor.departmentDepartment of Microbiology and Physiological Systems


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