A single peptide-major histocompatibility complex ligand triggers digital cytokine secretion in CD4(+) T cells.
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.
Duke Scholars
Altmetric Attention Stats
Dimensions Citation Stats
Published In
DOI
EISSN
Publication Date
Volume
Issue
Start / End Page
Location
Related Subject Headings
- Tumor Necrosis Factor-alpha
- T-Lymphocyte Subsets
- Single-Cell Analysis
- Secretory Rate
- Receptors, Antigen, T-Cell, alpha-beta
- Quantum Dots
- Peptide Fragments
- Moths
- Molecular Sequence Data
- Lymphocyte Activation
Citation
Published In
DOI
EISSN
Publication Date
Volume
Issue
Start / End Page
Location
Related Subject Headings
- Tumor Necrosis Factor-alpha
- T-Lymphocyte Subsets
- Single-Cell Analysis
- Secretory Rate
- Receptors, Antigen, T-Cell, alpha-beta
- Quantum Dots
- Peptide Fragments
- Moths
- Molecular Sequence Data
- Lymphocyte Activation