What do superantigens bind to simultaneously to exert their effects?

Superantigens exert their effects by binding simultaneously to a T-cell receptor and an MHC class II molecule. This unique interaction allows superantigens to bypass the normal antigen processing and presentation pathways, leading to the activation of a large number of CD4+ T cells regardless of their specificities.

In a typical immune response, T-cell receptors (TCRs) recognize specific peptides presented by MHC molecules, requiring precise matching between the TCR and the peptide-MHC complex. However, superantigens can simultaneously bind to the variable region of the TCR and to the MHC class II molecule on antigen-presenting cells. This results in the cross-linking of the TCR and MHC, leading to an excessive and uncontrolled activation of T cells.

This low specificity of stimulation can trigger a massive release of cytokines, resulting in systemic effects often associated with toxic shock and other severe immune responses. Understanding this mechanism underscores the potential dangers associated with superantigens, which can be produced by certain bacteria such as Staphylococcus aureus or Streptococcus pyogenes.