RT Journal Article
SR Electronic
T1 Signal Transduction Through a DNA-Based T Cell Receptor
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 062877
DO 10.1101/062877
A1 Marcus J. Taylor
A1 Kabir Husain
A1 Zev J. Gartner
A1 Satyajit Mayor
A1 Ronald D. Vale
YR 2016
UL http://biorxiv.org/content/early/2016/07/08/062877.abstract
AB T cells mount an immune response based upon the strength of the interaction between its T cell receptor (TCR) and peptide-loaded MHCs (pMHC) on an antigen-presenting cell. How T cells become activated by some pMHCs, but not others with slightly shorter bound times, remains an unanswered question. Here, we developed a finely tunable synthetic receptor-ligand system in which the extracellular domains of the TCR and pMHC were replaced with two short hybridizing strands of DNA. Remarkably, the T cell signaling response can discriminate between DNA ligands differing by a single base pair. Single molecule imaging reveals that ligated receptors with longer bound times promote the binding of more ligands nearby to create clusters; stable clusters of 2-4 ligated receptors then trigger receptor phosphorylation and signaling. These results reveal how T cells convert the bound time of an extracellular receptor-ligand interaction into a physical reorganization of molecules in the membrane and intracellular signaling.