Shared promoter elements between a viral superantigen and the major histocompatibility complex class II-associated...

Superantigens have the ability to stimulate subsets of T lymphocytes bearing particular T-cell receptor Vbeta chains. The best-known viral superantigen is Mls, a product of the murine mammary tumor virus (MMTV) sag gene. The MMTV superantigen is not displayed by the virus itself; however, after infection of B lymphocytes, the superantigen is expressed. The resulting immune stimulation is essential for viral transmission. We have analyzed the transcriptional elements which control Mls-1 expression. Here we present evidence that a region at the 3' end of Mtv-7 env, Penv2, controls B-cell-specific expression of sag. Penv2 has elements homologous with promoters of immunoglobulin H chain, the invariant chain, and major histocompatibility complex class II, suggesting a coordinate regulation of expression of these various B-cell-specific genes and indicating a possible eukaryotic origin of MMTV sag. We have determined that both an IgH heptamer element and a Y box are essential for Penv2 promoter activity and that tandem octamer motifs in the U3 region of the 3' MMTV long terminal repeat function as enhancers. We propose that Penv2 controls constitutive Mls expression in B lymphocytes.