Force awakens the dark side of T cell autoimmunity

T cell activation is governed by the interaction of the T cell receptor (TCR) with antigenic peptide:MHC (pMHC) that are found in the surface membranes of T cells and APCs. Protein interactions that occur between opposing cells are constrained to two dimensions (2D). To understand T cell activation and the process of antigen recognition, we have defined the 2D kinetics of affinity and bond lifetime that occurs under forces between TCR and pMHC. These data support that the 2D kinetics determines the fate of the T cell and provides potential mechanisms for regulating autoimmune disease and anti-tumor responses.