Data from: A Higher Activation Threshold of Memory CD8+ T Cells Has a Fitness Cost That Is Modified by TCR Affinity during Tuberculosis
UMass Chan AffiliationsDepartment of Microbiology and Physiological Systems
Cytotoxic T cells
Memory T cells
Vaccination and immunization
Immunology of Infectious Disease
Immunoprophylaxis and Therapy
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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.
Permanent Link to this Itemhttp://hdl.handle.net/20.500.14038/36444
Data collection dates: 2014-2015. Methodology is documented in published manuscript.
Funding and AcknowledgementsNational Institute of Allergy and Infectious Diseases, National Institutes of Health, U.S. Department of Health and Human Services; R01 AI106725
This dataset is the primary data source for the following published study: Carpenter SM, Nunes-Alves C, Booty MG, Way SS, Behar SM. A Higher Activation Threshold of Memory CD8+ T Cells Has a Fitness Cost That Is Modified by TCR Affinity during Tuberculosis. PLoS Pathog. 2016 Jan 8;12(1):e1005380. doi:10.1371/journal.ppat.1005380. eCollection 2016 Jan. PubMed PMID: 26745507; PubMed Central PMCID: PMC4706326.