The superantigen SEA binds to human γS T cell receptor and activates γS T cells with moderate MHC class II dependence

Bacterial toxins, called superantigens, are produced by Staphylococcus aureus and are known to activate gamma S T cells. gamma S T cells contribute to long-lasting immunity against bacterial skin infections caused by S. aureus. gamma S T cells are a distinct subgroup of T cells containing the T cell receptor (TCR) gamma and S chains. The gamma S TCR harbouring the variable chains TRGV9/TRDV2 is the most common TCR in human peripheral blood and is known to be activated by superantigens and are also promising candidates for tumor immunotherapy. However, detailed analyses of antigen binding to gamma S TCR have been severely hampered by difficulties in producing large amounts of gamma S TCR. In this study, we report a protocol to produce recombinant gamma S TCR (TRGV9/TRDV2) by fusing the variable domains gamma S TCR with the constant domains of alpha(3 TCR. Subsequently, binding analyses were executed applying microscale thermophoresis showing a clear binding between superantigen and the gamma S TCR in the micro molar range. In addition, the superantigen SEA was shown to induce cytokine expression in gamma S T cells with moderate MHC dependence, suggesting that other receptors can act as antigen presenting molecules upon gamma S T cell activation. These results pave the way towards a better understanding of superantigen recognition by the gamma S T cells and facilitates the future use of gamma S TCR in cellular tumor immunotherapy.