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Laboratoire d’Immunologie, Département de Microbiologie et Immunologie, Université de Montréal, Montréal, Canada;
Department of Experimental Medicine, McGill School of Medicine, Montréal, Canada;
Laboratoire d’Immunologie, Centre de Recherche du Centre Hospitalier de l’Université de Montréal, Montréal, Canada;
Department of Microbiology and Immunology, McGill University, Montréal, Canada;
¶ Institut Pasteur, Unité d’Immunochimie Analytique, Paris, France; and
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Laboratoire d’Immunologie Moléculaire, Université de Montréal, Montréal, Canada
The binding of bacterial superantigens (SAgs) is profoundly affected by the nature of the MHC class II-associated antigenic peptide. It was proposed that 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 quantitatively the size of this SAg-receptive pool of HLA-DR molecules that are available to bind and present staphylococcal enterotoxin A (SEA) at the surface of B lymphocytes. Our binding curves, depletion experiments, and quantitative immunoprecipitations show that about half the HLA-DR class II molecules 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 presented to T cells. This characteristic appears to be necessary for SAg-induced T cell apoptosis. When <0.3% of the total cell surface MHC class II molecules are occupied by SEA, T cells undergo a normal sequence of early activation events. However, presentation of a ligand density beyond this threshold results in T cell activation that is readily aborted by apoptosis but only 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 quantitative framework to account for the ability of bacterial SAgs to induce peripheral activation vs tolerance in the host.
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