Publications by authors named "Ian R Fallahee"
Article Synopsis
- Self-non-self discrimination is a key part of how T cells work in our immune system.
- A specific process involving a protein called LAT and a part of it called Y132 is really important for T cells to tell the difference between what’s friendly and what’s harmful.
- Changing a nearby part of LAT can speed up this process, making T cells better at responding to weaker signals, which helps them act more accurately when fighting infections.
The sequence of events that initiates T cell signaling is dictated by the specificities and order of activation of the tyrosine kinases that signal downstream of the T cell receptor. Using a platform that combines exhaustive point-mutagenesis of peptide substrates, bacterial surface-display, cell sorting, and deep sequencing, we have defined the specificities of the first two kinases in this pathway, Lck and ZAP-70, for the T cell receptor ζ chain and the scaffold proteins LAT and SLP-76. We find that ZAP-70 selects its substrates by utilizing an electrostatic mechanism that excludes substrates with positively-charged residues and favors LAT and SLP-76 phosphosites that are surrounded by negatively-charged residues.
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