Editors' ChoiceImmunology

Higher Avidity Binding by Activated T Cells

STKE  27 Mar 2001:
Vol. 2001, Issue 75, pp. tw14
DOI: 10.1126/stke.2001.75.tw14

Naïve T cells that have not been exposed to antigen require high amounts of antigen and costimulation in order to activate a response. However, activated T cells can respond to very small amounts of antigen. Fahmy et al. explored the mechanism underlying this difference by monitoring the interaction of T cell receptor (TCR)/CD8 complex with fluorescently labeled, divalent major histocompatibility complexes (MHCs). The binding curves were different for naïve and activated T cells with the activated T cells exhibiting enhanced binding at lower concentrations of MHC. The increased binding was blocked by the addition of an antibody (H57) that blocked TCR cross-linking, but did not interfere with MHC binding. This cross-linking event is not the same as the formation of the immunologic synapse, because H57 does not impair the formation of the synapse. The differences between naïve and activated T cells were also influenced by the presence of the membrane microdomain, known as the lipid raft, because higher concentrations of cholesterol increased the avidity of naïve T cell binding and decreased cholesterol or sphingomyelin depletion decreased the avidity of the activated T cells. Modeling of the binding data suggest that the activated TCR has a 50-fold increase in avidity at 4(C and a 15- to 20-fold increase at 37(C as compared with the TCR from naïve T cells.

T. M. Fahmy, J. G. Bieler, M. Edidin, J. P. Schneck, Increased TCR avidity after T cell activation: A mechanism for sensing low-density antigen. Immunity 14, 135-143 (2001). [Online Journal]