Generated Single Point-Mutations Can Considerably Dismantle the Lymphocyte Overstimulation Induced byYersinia pseudotuberculosisSuperantigen

The superantigenicYersinia pseudotuberculosis-derived mitogen (YPM) may contribute to severe complications inY. pseudotuberculosisinfections. Since the pathogenic mechanism of a superantigen (SAg) is based on its capability for T-cell overstimulation, by introducing point mutations into YPM an attempt was made to abrogate this effect. Six mutants studied exhibited a variety of T-cell proliferating responses. Two had activity reduced by 80–90%, three had activity reduced by ∼50%, and one mutant showed almost no attenuation. The SAg-associatedin vitropathogenic functions, cytotoxic activation and the production of proinflammatory cytokines, were also diminished, in parallel. Since these mutants were confirmed to be defective in TCR Vβ binding, it was possible to compare them with native YPM. Our results suggested that the intensity of TCR Vβ binding is a crucial factor determining the severity of pathogenesis and that single amino acid alterations might be useful for producing immunotherapeautical agents from native YPM.