Directed Evolution of T-Cell Receptors for Binding Superantigens

A T-cell recognizes two major classes of antigens. Binding of the αβ T-cell receptor (TCR) to an intracellularly-processed peptide antigen in the context of a major histocompatibility complex (pMHC) provides for the specificity of a cell-mediated immune response. However, this normal antigen recognition event can be circumvented by bacterial and viral proteins called superantigens (SAgs) (1 ). These unprocessed antigens bind to and thereby crosslink the variable region of the TCR β chain (V_β ) with a class II pMHC product, resulting in stimulation of a large subset of T cells. This nonspecific immune response results in detrimental inflammatory reactions, T-cell deletion, and/or T-cell anergy (2 ,3 ).