We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
A Higher Activation Threshold of Memory CD8<sup>+</sup> T Cells Has a Fitness Cost That Is Modified by TCR Affinity during Tuberculosis.
- Authors
Carpenter, Stephen M.; Nunes-Alves, Cláudio; Booty, Matthew G.; Way, Sing Sing; Behar, Samuel M.
- 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.
- Subjects
T cells; VACCINE research; MYCOBACTERIUM tuberculosis; PATHOGENIC microorganisms; CD8 antigen; T cell receptors; VACCINATION
- Publication
PLoS Pathogens, 2016, Vol 12, Issue 1, p1
- ISSN
1553-7366
- Publication type
Article
- DOI
10.1371/journal.ppat.1005380