The enhancement of proinflammatory responses to LPS by superantigens in PBMCs is not dependent on superantigen ligation of TCR or IFN-γ production. (A) Enhancement of LPS-induced TNF-α production was supported by TCR nonbinding but not MHC class II nonbinding SEA constructs. Cells were exposed to SEA constructs (1 ng/mL) for 3 hours, then coincubated with LPS (1 ng/mL) for an additional 4 hours. Mean and SD of triplicate stimulations are shown and data are representative of 5 experiments. (B) T-cell mitogenic potential of SEA WT versus mutant constructs was confirmed in 3 donors. (C) Anti–IFN-γ did not inhibit enhanced production of TNF-α by PBMCs following superantigen-LPS exposure. ITMC indicates isotype-matched control antibody. Mean and SD of triplicate samples are shown; data are representative of 5 separate experiments.