BINDING-SITES FOR BACTERIAL AND ENDOGENOUS RETROVIRAL SUPERANTIGENS CAN BE DISSOCIATED ON MAJOR HISTOCOMPATIBILITY COMPLEX CLASS-II MOLECULES

Bacterial and retroviral superantigens (SAGs) interact with major hist ocompatibility complex (MHC) class II molecules and stimulate T cells upon binding to the V beta portion of the T cell receptor. Whereas bot h types of molecules exert similar effects on T cells, they have very different primary structures. Amino acids critical for the binding of bacterial toxins to class II molecules have been identified but little is known of the molecular interactions between class II and retrovira l SAGs. To determine whether both types of superantigens interact with the same regions of MHC class II molecules, we have generated mutant HLA-DR molecules which have lost the capacity to bind three bacterial toxins (Staphylococcus aureus enterotoxin A [SEA], S. aureus enterotox in B [SEB], and toxic shock syndrome toxin 1 [TSST-1]). Cells expressi ng these mutated class II molecules efficiently presented two retrovir al SAGs (Mtv-9 and Mtv-7) to T cells while they were unable to present the bacterial SAGs. These results demonstrate that the binding sites for both types of SAGs can be dissociated.