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

Abstract

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 Vβ-specific T-cell subsets¹. SEA interacts with class II major histocompatibility complex (MHC) antigens on antigen-presenting cells and the T-cell antigen receptor (TCR) on T cells^2–4, resulting in a ternary complex of MHC–SEA–TCR. Mis antigens are known to be products of mouse mammary tumour virus (MMTV)^5,6, 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^7,8; 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.