Increased MHC H–2K gene transcription in cultured mouse embryo cells after adenovirus infection

Abstract

The class I major histocompatibility complex (MHC) antigens are highly polymorphic cell-surface proteins whose expression is essential for the cellular immune response against virus-infected, abnormal and foreign cells. Transformation of primary rat cell cultures by the oncogenic adenovirus 12 (Ad12) results in suppression of the transplantation antigens, thus enabling the transformed cells to escape the immune response and efficiently form tumours in vivo. In contrast, transformation of the same cells with the non-oncogenic adenovirus 5 (Ad5) does not suppress the transplantation antigens and, consequently, they elicit an effective (MHC-restricted) immune response. Here, however, we show that infection of mouse embryo cells with both viruses initially increases the level of transcripts from the H-2Kb transplantation antigen gene. Both the adenovirus E1a (12S RNA) and E1b genes are required for activation of the H-2K gene and measurement of the relative rate of transcription indicates that the increase in the level of H-2K messenger RNA following infection is at least in part due to a gene-specific transcriptional activation. The newly transcribed H-2Kb mRNA is then properly transported to the cytoplasm.

Adenovirus E1A-mediated regulation of class I MHC expression.

“…Finally, the results presented in this study seem to contradict those of Rosenthal et al (1985), who showed that infection of mouse embryo cultures with AdS as well as with Adl2 results in strong stimulation of class I MHC mRNA expression. Their observation has been confirmed (B.Oostra, personal communication), but we have no explanation for the apparently opposite effects on class I gene expression of Adl2 in transformation and lytic infection.…”

Adenoviruses of subgenera B, C, D, and E modulate cell-surface expression of major histocompatibility complex class I antigens.

“…This is achieved in spite of an increase in transcription of class I genes docu- mented for AdS and Adl2 during infection of mouse embryo cells (38). The reduction in cell-surface class I antigen expression is in all cases probably due to a viral protein that physically binds to class I antigens and abrogates their intracellular transport.…”

Two purified factors bind to the same sequence in the enhancer of mouse MHC class I genes: one of them is a positive regulator induced upon differentiation of teratocarcinoma cells

“…This regulation involves activation of both beta-2-microglobulin and H-2 genes, and is likely to operate at the transcriptional level (5,9). It has been reproduced after transfection of Nucleic Acids Research EC cells by a cloned H-2 gene (10). Fusion experiments between undifferentiated EC and differentiated cells have given conflicting results as to whether positive or negative regulation is involved (11,12).…”