Ron Vale, Ph.D.
Professor, University of California, San Francisco
HHMI Investigator

Abstract:
A T cell-mediated immune response is initiated by the T cell receptor (TCR) interacting with peptide-bound MHC (pMHC) on an infected cell. The mechanism by which this interaction triggers intracellular phosphorylation of the TCR, which lacks a kinase domain, remains poorly understood. We have approached this problem through a reconstitution strategy. The TCR and associated signalling molecules were introduced into a non-immune cell, and we showed that this "artificial T cell" can exhibit ligand-specific signalling when conjugated with an antigen presenting cell. Using this system, we were able to dissect the roles of different components in this signaling process and suggest a mechanism for how the T cell receptor works.