A SIGNALING PATHWAY COUPLED TO T-CELL RECEPTOR LIGATION BY MMTV SUPERANTIGEN LEADING TO TRANSIENT ACTIVATION AND PROGRAMMED CELL-DEATH

Stimulation of T cells by retroviral and bacterial superantigens is followed by specific T cell elimination, in contrast with stimulation of T cells by peptide, which is usually associated with clonal expansion. We show here that this differential response phenotype is apparent at the level of individual T cell clones following TCR ligation with peptide or MTV antigen. We exploited selective coupling of apoptosis to TCR ligation by MTV7 to examine some of the intracellular biochemical events that underlie this response. MTV-dependent activation resulting in apoptosis was associated with activation of phospholipase Aa and the generation of reactive oxygen intermediates. Inhibition of these biochemical events prevented both MTV-dependent activation and apoptosis without affecting the peptide-dependent response of the same T cell clones. These results indicate that clonal expansion or programmed cell death following TCR ligation may be consequences of distinct TCR-coupled signaling pathways.