Project Summary/Abstract T cells utilize surface-bound T cell receptors (TCR) at the immunological synapse with antigen-presenting cells (APC). Detection of their peptide-MHC ligands results in rapid intracellular signaling, necessary for acquisition of effector functions and for profound adaptive immunity. While we now understand some of the fundamental proteins in this processing, understanding how each works together in the context of a rapidly moving T cell has proven difficult. TCR recognition happens as surface deformations provide initial contact. However, despite various fixed and lower-resolution approaches to understanding this process, it has not been previously possible to study this complete surface in real-time in the full 3-dimensions in which it takes place. Here, we will use novel and advanced imaging approaches to define how cytoskeletally-driven membrane movements provide a backbone for efficient ligand detection and we will describe how a range of widely variant environmental cues as well as novel pathways alter this process and affect immune surveillance. This project will define how T cells effectively `find' their ligands amidst a sea of competing MHC. This efficiency of search and detection has clear implications for the ability of T cells to discovery rare epitopes and initiate a response, for example during the early phases of a viral infection.
NIH ExPorter
NIH ExPorter