Bacterial and retroviral superantigens share a common binding region on class II MHC antigens

Staphylococcal enterotoxin A (SEA), one of the most potent T-cell mitogens known, has been classified as a bacterial superantigen on the basis of ability to stimulate V beta-specific T-cell subsets. SEA interacts with class II major histocompatibility complex (MHC) antigens on antigen-presenting cells and the T-cell antigen receptor (TCR) on T cells, resulting in a ternary complex of MHC-SEA-TCR. Mls antigens are known to be products of mouse mammary tumour virus (MMTV), and it has been reported that two exogenous strains of MMTV encode retroviral superantigens in the open reading frames of the 3' long terminal repeat of the viral genome; however, no binding of the putative MMTV superantigen to either MHC antigens or TCR has been demonstrated. Here we use synthetic peptides to identify a site on the MMTV-1 superantigen that binds to class II MHC antigens. The site is encompassed by amino-acid residues 76-119 of the MMTV-1 superantigen. Direct binding and competition experiments show that the MMTV superantigen and SEA bind to at least one common region on class II MHC antigens.