A cartoon of what might be happening at the immunological synapse during Sag engagement.

In a model consistent with the crystal complexes shown in Figure 1, CD28 provides the essential 2nd co-stimulatory signal through separate B7 ligation. CD28 is essential for Sag toxicity [11],[12]. In the new model proposed on the right, CD28 is part of a larger more stable complex directly ligated by Sag. This new model explains much better the extreme potency and cytokine toxicity observed with Sags. In theory this tetrameric complex would be more stable being held together by 3 interactions rather than 2.