IMPORTANCE OF ACIDIC, PROLINE SERINE/THREONINE-RICH, AND GTP-BINDING REGIONS IN THE MAJOR HISTOCOMPATIBILITY COMPLEX CLASS-II TRANSACTIVATOR - GENERATION OF TRANSDOMINANT-NEGATIVE MUTANTS/

The class II transactivator (CIITA) is a master transcription regulato r of gene products involved in the exogenous antigen presentation path way, including major histocompatibility complex (MHC) class II, invari ant chain, and DM, An extensive analysis of the putative functional do mains of CIITA is undertaken here to explore the action of CIITA, Anti bodies to CIITA protein were produced to verify that these mutant prot eins are expressed. Both acidic and proline/serine/threonine-rich doma ins are essential for class II MHC promoter activation. In addition, t hree guanine nucleotide-binding motifs are essential for CIITA activit y, Of these mutants, two exhibited strong transdominant-negative funct ions. These two mutants provide a plausible approach to manipulate MHC class II expression and immune responses.