Tat competes with CIITA for the binding to P-TEFb and blocks the expression of MHC class II genes in HIV infection

AIDS and the bare lymphocyte syndrome (BLS) are severe combined immunodefic iencies. BLS results from mutations in genes that regulate the expression o f class II major histocompatibility (MHC II) determinants. One of these is the class II transactivator (CIITA). HIV and its transcriptional transactiv ator (Tat) also block the expression of MHC II genes. By binding to the sam e surface in the cyclin T1, which together with CDK9 forms the positive tra nscription elongation factor b (P-TEFb) complex, Tat inhibits CIITA. CIITA can also activate transcription when tethered artificially to RNA. Moreover , a dominant-negative CDK9 protein inhibits the activity of MHC II promoter s. Thus, CIITA is a novel cellular coactivator that binds to P-TEFb for the expression of its target genes.