Induction of the murine class-II antigen-associated invariant chain by TNF-alpha is controlled by an NF-kappa B-like element.

The murine class-II antigen-associated invariant chain (Ii) is a glycoprotein whose synthesis is co-regulated with the major histocompatibility class-II antigens. The Ii mRNA is inducible by tumor necrosis factor-alpha (TNF-alpha). An NF-kappa B protein-binding site (NBS), located in the Ii promoter at bp -121 to -111, confers TNF-alpha inducibility on chimeric reporter constructs expressing the human growth hormone-encoding gene. A distal NF-kappa B-like protein-binding site (NBLS) located at bp -167 to -157 is not required for TNF-alpha inducibility, and deletion of this distal NBLS results in increased constitutive, as well as TNF-alpha-induced, expression of the reporter gene. The NBS is well protected during DNase I footprinting assays and specifically binds proteins in electrophoretic mobility shift assays. A distinct protein-DNA complex is observed when nuclear extracts from TNF-alpha-treated L-cells are used; this complex is not seen in extracts from untreated cells.