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Immunity. 2013 Nov 14;39(5):846-57. doi: 10.1016/j.immuni.2013.08.036. Epub 2013 Oct 10.

A single peptide-major histocompatibility complex ligand triggers digital cytokine secretion in CD4(+) T cells.

Author information

1
Department of Microbiology and Immunology, Stanford University, Stanford, CA 94305, USA.

Abstract

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-α (TNF-α) and interleukin-2 (IL-2) cytokines with a rate of ∼1,000, ∼10,000, and ∼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.

PMID:
24120362
PMCID:
PMC3846396
DOI:
10.1016/j.immuni.2013.08.036
[Indexed for MEDLINE]
Free PMC Article

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