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

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Huang, J; Brameshuber, M; Zeng, X; Xie, J; Li, Q-J; Chien, Y-H; Valitutti, S; Davis, MM

Published Date

  • November 2013

Published In

Volume / Issue

  • 39 / 5

Start / End Page

  • 846 - 857

PubMed ID

  • 24120362

Pubmed Central ID

  • 24120362

Electronic International Standard Serial Number (EISSN)

  • 1097-4180

International Standard Serial Number (ISSN)

  • 1074-7613

Digital Object Identifier (DOI)

  • 10.1016/j.immuni.2013.08.036

Language

  • eng