Identification of an interferon-gamma-responsive element of a class II major histocompatibility gene in rat type 1 astrocytes.

Interferon-gamma(IFN-gamma) has been shown to induce class II major histocompatibility complex (MHC) antigens on several cell types. Previous analysis of cell lines including a glioblastoma multiforme line by our laboratory has mapped an IFN-gamma-responsive element to the upstream - 141 to - 109 base pair (bp) region of the DRA promoter. Using deletion mutants, this report shows that this same general region (-135 to -109 bp) is important for IFN-gamma induction in two other human glioma lines and more importantly in primary astrocytes. We have confirmed that this regulatory region of the HLA-DRA gene is necessary for IFN-gamma inducibility in astrocytes using a substitution mutant. Sequences beyond -135 bp do not appear to have any additional positive or negative elements.