Increased TCR avidity after T cell activation: A mechanism for sensing low-density antigen

While activated T cells are known to have enhanced biological responses to antigen stimulation, the biophysical basis of this increased sensitivity re mains unknown. Here, we show that, on activated T cells, the TCR avidity fo r peptide-MHC complexes is 20- to 50-fold higher than the TCR avidity of na ive T cells. This increased avidity for peptide-MHC depends on TCR reorgani zation and is sensitive to the cholesterol content of the T cell membrane. Analysis of the binding data indicates the enhanced avidity is due to incre ases in cross-linking of TCR on activated T cells. Activation-induced membr ane (AIM) changes in TCR avidity represent a previously unrecognized means of increasing the sensitivity of activated T cells to small amounts of anti gen in the periphery.