Two distinct domains within CIITA mediate self-association: Involvement ofthe GTP-binding and leucine-rich repeat domains

CIITA is the master regulator of class II major histocompatibility complex gene expression. We present evidence that CIITA can self-associate via two domains: the C terminus (amino acids 700 to 1130) and the GTP-binding domai n (amino acids 336 to 702). Heterotypic and homotypic interactions are obse rved between these two regions. Deletions within the GTP-binding domain tha t reduce GTP-binding and transactivation function also reduce self-associat ion. In addition, two leucine residues in the C-terminal leucine-rich repea t region are critical for self-association as well as function. This study reveals for the first time a complex pattern of CIITA self-association. The se interactions are discussed with regard to the apoptosis signaling protei ns, Apaf-1 and Nod1, which share domain arrangements similar to those of CI ITA.