Quantitative relationship between MHC class II-Superantigen complexes and the balance of T cell activation versus death

The binding of bacterial superantigens (SAgs) is profoundly affected by the nature of the MHC class II-associated antigenic peptide. It was proposed t hat this limitation in the density of SAgs displayed at the surface of APCs is important for efficient TCR serial triggering as well as for preventing apoptosis of the responding T lymphocytes. Here, we have addressed quantit atively the size of this SAg-receptive pool of HLA-DR molecules that are av ailable to bind and present staphylococcal enterotoxin A (SEA) at the surfa ce of B lymphocytes. Our binding curves, depletion experiments, and quantit ative immunoprecipitations show that about half the HLA-DR class II molecul es on B cells are refractory to SEA binding. Yet, as compared with typical nominal Ags, an unusually high amount of class II-SAg complexes can be pres ented to T cells. This characteristic appears to be necessary for SAg-induc ed T cell apoptosis. When <0.3% of the total cell surface MHC class II mole cules are occupied by SEA, T cells undergo a normal sequence of early activ ation events. However, presentation of a ligand density beyond this thresho ld results in T cell activation that is readily aborted by apoptosis but on ly after a few cell divisions. Thus, we confirm the existence of MHC class II subsets that are structurally unable to present SEA and provide a quanti tative framework to account for the ability of bacterial SAgs to induce per ipheral activation vs tolerance in the host.