A cell topography-based mechanism for ligand discrimination by the T cell receptor
Fernandes RA., Ganzinger KA., Tzou JC., Jönsson P., Lee SF., Palayret M., Santos AM., Carr AR., Ponjavic A., Chang VT., Macleod C., Lagerholm BC., Lindsay AE., Dushek O., Tilevik A., Davis SJ., Klenerman D.
Significance One approach to testing biological theories is to determine if they are predictive. We have developed a simple, theoretical treatment of T cell receptor (TCR) triggering that relies on just two physical principles: ( i ) the time TCRs spend in cell–cell contacts depleted of large tyrosine phosphatases and ( ii ) constraints on the size of these contacts imposed by cell topography. The theory not only distinguishes between agonistic and nonagonistic TCR ligands but predicts the relative signaling potencies of agonists with remarkable accuracy. These findings suggest that the theory captures the essential features of receptor triggering.