THE DMB PROMOTER - DELINEATION, IN-VIVO FOOTPRINT, TRANSACTIVATION, AND TRANSDOMINANT SUPPRESSION

The HLA-DM loci encode the heterodimeric unconventional class II MHC m olecules that are coexpressed with conventional class II MHC molecules , DM molecules are essential for the proper formation and function of conventional class II MHC molecules, This report characterizes the DMB promoter both by in vivo footprint and by in vitro functional analysi s and reveals a promoter structure similar to that of conventional cla ss II MHC genes, DR-negative mutant cell lines selectively defective i n the transcription factor or class II trans-activator (CIITA) were us ed to reveal a requirement for both these factors in DMB promoter acti vation, Complementation of defective cell lines with the appropriate t ranscription factor reconstituted DMB promoter activation, Further ana lysis with CIITA identified several mutant forms of CIITA that are tra ns-dominant-negative mutants, i.e., they suppressed DMB promoter activ ation by transfected and endogenous CIITA, These mutants may be used i n a biological setting to down-regulate the function of DM in Ag proce ssing.