Human and Murine Clonal CD8+ T Cell Expansions Arise during Tuberculosis Because of TCR Selection
While T cells are required for protection against Mycobacterium tuberculosis infection, attempts to prevent tuberculosis by vaccines designed to elicit memory T cells have only been partially successful. Several vaccine candidates are in clinical trials, but progress has been slow because their ability to prevent disease must be empirically tested. There is little understanding of why certain antigens are targets of protective immunity. We have characterized an immunodominant CD8+ T cell response to the M. tuberculosis antigen TB10.4 (EsxH). CD8+ T cells specific for the TB10.44–11 epitope are primed early during infection and account for 30–50% of lung CD8+ T cells during chronic infection. Now we have used deep sequencing to characterize the TCR repertoire of TB10.44-11-specific CD8+ T cells in the lungs of infected mice. Interestingly, TB10.44-11-specific CD8+ T cells exhibit extreme clonal expansion of certain TCRβ with common structural features, most likely because of affinity selection. Affinity selection of T cells is more important when antigen presentation is limiting. Although the lung contains numerous bacteria during infection, antigen-presentation by infected APC may be limiting, mimicking a “low antigen” state. Thus, even T cells that have the potential to mediate protection may function inefficiently because of suboptimal T cell activation.
Vyšlo v časopise:
Human and Murine Clonal CD8+ T Cell Expansions Arise during Tuberculosis Because of TCR Selection. PLoS Pathog 11(5): e32767. doi:10.1371/journal.ppat.1004849
Kategorie:
Research Article
prolekare.web.journal.doi_sk:
https://doi.org/10.1371/journal.ppat.1004849
Souhrn
While T cells are required for protection against Mycobacterium tuberculosis infection, attempts to prevent tuberculosis by vaccines designed to elicit memory T cells have only been partially successful. Several vaccine candidates are in clinical trials, but progress has been slow because their ability to prevent disease must be empirically tested. There is little understanding of why certain antigens are targets of protective immunity. We have characterized an immunodominant CD8+ T cell response to the M. tuberculosis antigen TB10.4 (EsxH). CD8+ T cells specific for the TB10.44–11 epitope are primed early during infection and account for 30–50% of lung CD8+ T cells during chronic infection. Now we have used deep sequencing to characterize the TCR repertoire of TB10.44-11-specific CD8+ T cells in the lungs of infected mice. Interestingly, TB10.44-11-specific CD8+ T cells exhibit extreme clonal expansion of certain TCRβ with common structural features, most likely because of affinity selection. Affinity selection of T cells is more important when antigen presentation is limiting. Although the lung contains numerous bacteria during infection, antigen-presentation by infected APC may be limiting, mimicking a “low antigen” state. Thus, even T cells that have the potential to mediate protection may function inefficiently because of suboptimal T cell activation.
Zdroje
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Hygiena a epidemiológia Infekčné lekárstvo LaboratóriumČlánok vyšiel v časopise
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