Immobilized staphylococcal enterotoxin A is sufficient to induce T cell proliferation

We investigated the role of HLA-DR molecules in T cell stimulation by staphylococcal enterotoxin A (SEA). Previous results with immobilized purified HLA-DR preincubated with peptide showed that peptide-specific T cell clones were able to bind to and proliferate in response to purified HLA-DR/peptide complexes in the absence of antigen presenting cells. We report here that two human T cell clones (1 alpha beta and 1 gamma delta T cell clone) and a murine T cell hybridoma were each activated by immobilized purified HLA-DR4Dw4 preincubated with SEA. Furthermore, immobilized SEA in the absence of HLA-DR4Dw4 also stimulated the human T cell clones. The proliferative response of the human T cell clones was inhibited by CD3-reactive monoclonal antibodies, indicating that the T cell receptor (TCR)/CD3 reacts with SEA. These observations suggest that the HLA-DR in the complex functions only to immobilize SEA and that an interaction between the TCR and HLA-DR is not necessary for SEA-driven T cell stimulation. Finally, the assays described here could provide a method for defining and distinguishing the SEA binding sites for MHC class II and TCR.