Journal
IMMUNITY
Volume 39, Issue 5, Pages 846-857Publisher
CELL PRESS
DOI: 10.1016/j.immuni.2013.08.036
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Funding
- Howard Hughes Medical Institute
- US National Institutes of Health [R01 AI022511]
- Association pour la Recherche sur le Cancer [SL220100601347]
- Institut National du Cancer
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We have developed a single-molecule imaging technique that uses quantum-dot-labeled peptide-major histocompatibility complex (pMHC) ligands to study CD4(+) T cell functional sensitivity. We found that naive T cells, T cell blasts, and memory T cells could all be triggered by a single pMHC to secrete tumor necrosis factor-alpha (TNF-alpha) and interleukin-2 (IL-2) cytokines with a rate of similar to 1,000, similar to 10,000, and similar to 10,000 molecules/min, respectively, and that additional pMHCs did not augment secretion, indicating a digital response pattern. We also found that a single pMHC localized to the immunological synapse induced the slow formation of a long-lasting T cell receptor (TCR) cluster, consistent with a serial engagement mechanism. These data show that scaling up CD4(+) T cell cytokine responses involves increasingly efficient T cell recruitment rather than greater cytokine production per cell.
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