SERIAL TRIGGERING OF MANY T-CELL RECEPTORS BY A FEW PEPTIDE-MHC COMPLEXES

T LMPHOCYTES can recognize and be activated by a very small number of complexes of peptide with major histocompatibility complex (MHC) molec ules displayed on the surface of antigen-presenting cells (APCs)(1,2). The interaction between the T-cell receptor (TCR) and its ligand has low affinity and high off-rate(3-6). Both findings suggest that an ext remely small number of TCRs must be engaged in interaction with APCs a nd raise the question of how so few receptors can transduce an activat ion signal. Here we show that a small number of peptide-MHC complexes can achieve a high TCR occupancy, because a single complex can seriall y engage and trigger up to similar to 200 TCRs, Furthermore, TCR occup ancy is proportional to the T cell's biological response. Our findings suggest that the lovv affinity of the TCR can be instrumental in enab ling a small number of antigenic complexes to be detected.