Stimulation of all T cells bearing V_β1, V_β3, V_β11 and V_β12 by staphylococcal enterotoxin A

To determine the molecular mechanisms of T cell stimulation by staphylococcal enterotoxin A (SEA), we examined the expression of T cell receptor (TcR) V_β on the T cells from four strains of mice stimulated in vitro with SEA, using flow cytometric analysis for the number of T cells bearing V_β3, V_β6, V_β8, V_β11 and RNA blotting analysis for the amount of transcripts of V_β1, V_β5 and V_β12. The number of T cell blasts bearing V_β1, V_β3, V_β1 or V_β12 were increased in the T cell blasts proliferating in vitro in response to SEA in C57BL/6 mice. In AKR/J mice, which contain few V_β11‐ or V_β12‐bearing T cells due to a tolerance to the self‐MHC class II IE‐antigens, T cells bearing V_β1 or V_β3 responded to SEA. SEA enriched only V_β1‐bearing T cells in BALB/c mice carrying Mls‐2^a which lack Mls‐1^a‐reactive V_β3‐bearing T cells as well as V_β11‐ and V_β12‐bearing T cells. In spite of the presence of V_β1‐bearing T cells, C3H/He T cells exhibited a very low responsiveness to SEA. T cell repertoires skewed by clonal deletion of self‐reactive T cells may in part account for the different sensitivity to SEA among the different strains. A tolerance to SEA can be established in C57BL/6 mice which have been primed i.v. with SEA and treated i.p. with 200 mg/kg of cyclophosphamide 2 days later. All mature T cells bearing V_β3 or V_β11 were virtually abolished in the periphery of tolerant mice. These results suggest that most T cells reactive to SEA bear V_β1, V_β3, V_β11 or V_β12 and that clonal deletion of mature T cells reactive to SEA may account for the cellular mechanisms for cyclophosphamide‐induced tolerance to SEA.