T-CELL ACTIVATION DETERMINED BY T-CELL RECEPTOR NUMBER AND TUNABLE THRESHOLDS

The requirements for T cell activation have been reported io vary wide ly depending on the state of the T cell, the type of antigen-presentin g cell, and the nature of the T cell receptor (TCR) ligand. A unitary requirement for T cell responses was revealed by measurement of the nu mber of triggered TCRs. Irrespective of the nature of the triggering l igand, T cells ''counted'' the number of triggered TCRs and responded when a threshold of similar to 8000 TCRs was reached. The capacity to reach the activation threshold was severely compromised by a reduction in the number of TCRs. Costimulatory signals lowered the activation t hreshold to similar to 1500 TCRs, thus making T cells more sensitive t o antigenic stimulation.