Interferon Regulates Major Histocompatibility Class I Gene Expression through a 5′ Upstream Regulatory Region

Abstract

Major Histocompatibility complex (MHC) class I genes encode membrane glycoproteins involved in tissue rejection and T cell recognition of viral and foreign antigens. MHC class I gene expression is induced in a variety of cells by interferons (IFN) (both by IFN-α/β and by IFN-γ) (1–4). It is suggested that the increased MHC class I gene expression by IFNs plays a role in enhanced T cell immunity. However, the mechanisms of the IFN action in the induction of MHC class I gene expression have not been elucidated so far. Recently, Friedman and Stark reported the presence of ~30-bp IFN consensus sequence in the 5′ flanking region of IFN inducible genes which may be involved in IFN induced gene regulation (5). To study the molecular mechanism of MHC class I gene induction by IFNs, we tested promoter activity of the 5′ flanking region of a mouse MHC class I gene, H-2Ld. Various portions of the upstream region of the H-2Ld gene were connected to the chloramphenicol acetyltransferase (CAT) gene, and CAT activity was examined after transient and stable transfection of the genes into NIH 3T3 cells. We show that IFN treatment enhances promoter activity of the MHC class I gene, and that the IFN consensus sequence is responsible for the increased transcription of the gene.