Dendritic cell-specific MHC class II transactivator contains a caspase recruitment domain that confers potent transactivation activity

The MHC class II transactivator (CIITA) is a critical transcription factor that regulates genes involved in antigen presentation function. At least th ree functional forms of CIITA gene products are transcribed from three diff erent promoters. The CIITA gene expressed in dendritic cells (DC-CIITA) has a unique first exon encoding an extended N-terminal region of CIITA, Here, we show that the N terminus of DC-CIITA has high homology to a caspase rec ruitment domain (CARD) found in components of apoptosis and nuclear factor- KB signaling pathways. However, DC-CIITA does not regulate cell death, nor does it induce nuclear factor-KB activity. Instead, DC-CIITA is transcripti onally a more potent activator of the MHC class II gene than the form expre ssed in B cells. A single amino acid substitution in the CARD of DC-CIITA, predicted to disrupt CARD-CARD interactions, diminished the transactivation potential of DC-CIITA, These results indicate that the CARD in the context of CIITA serves as a regulatory domain for transcriptional activity and ma y function to selectively enhance MHC class II gene expression in dendritic cells.