The expression of major histocompatibility antigens under metallothionein gene promoter control.

A model system has been developed that provides insights into the mechanisms that control the amount of H-2 antigen on the cell surface. Hybrid genes have been constructed by using the metallothionein gene promoter to replace the H-2 gene promoter. The hybrid genes have been introduced into murine L cells and their expression has been studied. Cells containing the hybrid genes contain 20- to 60-fold more H-2 mRNA than nontransfected L cells, since the metallothionein gene promoter is much more active than the H-2 promoter. However, the total amount of H-2 antigen on the surface of the transfected L cell is similar to the amount of H-2 antigen on the normal L cell. Even after transcription from the metallothionein promoter is induced by the addition of cadmium to the cell culture medium, the amount of H-2 antigen on the surface of cells containing the hybrid genes does not increase. We conclude that the amount of H-2 antigen is controlled by events that occur after gene transcription. Evidence is presented that suggests that these post-transcriptional mechanisms may cause the expression of threefold more H-2Dd than H-2Ld on the surface of BALB/c cells. Furthermore, we suggest that the 5' untranslated portion of the H-2 mRNA is not important for directing the growing H-2 polypeptide to the cell surface.