Structural analysis of a mouse mammary tumor virus superantigen.

It has recently been shown that the minor lymphocyte stimulating-like products expressed by some mice are actually encoded by open reading frames in the 3' long terminal repeats of mouse mammary tumor viruses. These products act as viral superantigens (vSAGs). That is, they stimulate most T cells bearing particular V beta s almost regardless of the rest of the variable components of the T cell receptors expressed by those cells. To find out more about the structure of these vSAGs, a set of truncated vSAG genes was used in transfection and in vitro translation experiments to show that the functional vSAG is a type II integral membrane protein with a large glycosylated extracellular COOH-terminal domain and a small, nonessential, intracellular NH2-terminal cytoplasmic domain. These results are consistent with the fact that the vSAGs must be expressed on the cell surface in order to interact with T cells and class II major histocompatibility complex proteins. They also account for the finding that much of the V beta specificity of the vSAGs is controlled by amino acids at the COOH-terminal end of the vSAG proteins, amino acids that will be extracellular in type II proteins.