Direct binding of the Mtv7 superantigen (Mls-1) to soluble MHC class II molecules

The superantigen encoded by the mouse mammary tumor virus (MMTV) is a potent stimulator of T cells when bound to MHC class II molecules. Recent data from this laboratory have shown that the Mtv7 superantigen, Mls-1, elicits a strong T cell response when presented by HLA-DR. To expand these observations further, we have produced the 28 kDa extracellular domain and the 18 kDa carboxy-terminal subfragment of the Mls-1 protein in E. coli and studied their interaction with human MHC class II molecules in vitro. In this report, we demonstrate direct binding of these recombinant forms of the Mls-1 protein to soluble HLA-DR1 and HLA-DR4, but not to HLA-A2. Our data imply a unique class II interaction site of retroviral superantigens that is not shared with bacterial superantigens.