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Superantigens (SAGs) are a class of disease‐causing and immunostimulatory proteins of bacterial or viral origin that activate T cells by binding to the Vβ domain of the T‐cell antigen receptor (TCR), The three‐dimensional structure of the complex between a TCR β chain (mouse Vβ8.2‐Jβ2.l‐Cβ1) and the SAG staphylococcal enterotoxin d (SEC3) has been recently determined. The complementarity‐determining region 2 (CDR2) of the β chain and, to lesser extents, CDR1 and hypervariable region 4 (HV4) bind in a cleft between the small and large domains of the SAG, A model of the TCR‐SAG‐peptide/MHC complex constructed from available crystal structures reveals how the SAG acts as a wedge between the TCR and MHC, thereby displacing die antigen in peptide away from the TCR and circumventing the normal mechanism for T‐cell activation by peptide/MHC, To evaluate the actual contribution of individual …