T cell activation determined by T cell receptor number and tunable thresholds

The requirements for T cell activation have been reported io vary widely depending on the state of the T cell, the type of antigen-presenting cell, and the nature of the T cell receptor (TCR) ligand. A unitary requirement for T cell responses was revealed by measurement of the number of triggered TCRs. Irrespective of the nature of the triggering ligand, 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 threshold to similar to 1500 TCRs, thus making T cells more sensitive to antigenic stimulation.