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 glyco protein whose synthesis is co-regulated with the major histocompatibil ity class-II antigens. The Ii mRNA is inducible by tumor necrosis fact or-alpha (TNF-alpha). An NF-kappaB 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-e ncoding gene. A distal NF-KB-like protein-binding site (NBLS) located at bp -167 to -157 is not required for TNF-alpha inducibility, and del etion of this distal NBLS results in increased constitutive, as well a s TNF-alpha-induced, expression of the reporter gene. The NBS is well protected during DNase I footprinting assays and specifically binds pr oteins in electrophoretic mobility shift assays. A distinct protein-DN A complex is observed when nuclear extracts from TNF-alpha-treated L-c ells are used; this complex is not seen in extracts from untreated cel ls.