Transcriptional activation of HLA-DR alpha by interferon gamma requires a trans-acting protein.

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Abstract
Stimulation of the human epithelial-like cell line, HeLa, with interferon .gamma. (IFN-.gamma.) induces steady-state levels of HLA-DR.alpha. mRNA. Using a sensitive RNase-mapping procedure, we detect induced HLA-DR.alpha. mRNA as early as 8 hr after IFN-.gamma. treatment; maximal accumulation occurs by 48 hr. Treatment with the protein synthesis inhibitor, cycloheximide, abolishes the IFN-.gamma.-induced accumulation of HLA-DR.alpha. mRNA, indicating that de novo synthesis of a trans-acting protein factor is required for induction of this major histocompatibility complex class II gene. Nuclear run-off transcription assays revealed that IFN-.gamma. acts by directly stimulating the transcription rate of HLA-DR.alpha.. Similarly, IFN-.gamma. increased the transcription rate of the class I HLA-A2-encoding gene as well as that of the human invariant chain gene. IFN-.gamma.-induced transcription of HLA-DR.alpha. and of the invariant chain gene was blocked by treatment with cycloheximide, but IFN-.gamma.-induced transcription of HLA-A2 was unaffected. Our findings show that transcriptional induction of HLA-DR.alpha. and the invariant chain gene by IFN-.gamma. requires the action of an unidentified trans-acting protein.