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

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-? (TNF-?) 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.

SUBMITTER: Huang J 

PROVIDER: S-EPMC3846396 | biostudies-literature | 2013 Nov

REPOSITORIES: biostudies-literature