Tat Competes With CIITA for the Binding to P-TEFb and Blocks the Expression of MHC Class II Genes in HIV Infection

Immunity. 2000 Jan;12(1):61-70. doi: 10.1016/s1074-7613(00)80159-4.

Abstract

AIDS and the bare lymphocyte syndrome (BLS) are severe combined immunodeficiencies. BLS results from mutations in genes that regulate the expression of class II major histocompatibility (MHC II) determinants. One of these is the class II transactivator (CIITA). HIV and its transcriptional transactivator (Tat) also block the expression of MHC II genes. By binding to the same surface in the cyclin T1, which together with CDK9 forms the positive transcription 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 promoters. Thus, CIITA is a novel cellular coactivator that binds to P-TEFb for the expression of its target genes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigen Presentation / immunology
  • B-Lymphocytes / immunology
  • Cells, Cultured
  • Cyclin T
  • Cyclin-Dependent Kinase 9
  • Cyclin-Dependent Kinases / metabolism
  • Cyclins / genetics
  • Cyclins / metabolism
  • Enterotoxins / immunology
  • Gene Products, tat / genetics
  • Gene Products, tat / metabolism*
  • Genes, MHC Class II*
  • HIV Infections / metabolism*
  • HIV-1 / immunology
  • HLA-DR Antigens / genetics*
  • Humans
  • Nuclear Proteins*
  • Positive Transcriptional Elongation Factor B
  • Promoter Regions, Genetic
  • Protein-Serine-Threonine Kinases / metabolism*
  • Superantigens / immunology
  • Trans-Activators / genetics
  • Trans-Activators / metabolism*
  • Transcriptional Activation
  • tat Gene Products, Human Immunodeficiency Virus

Substances

  • CCNT1 protein, human
  • Cyclin T
  • Cyclins
  • Enterotoxins
  • Gene Products, tat
  • HLA-DR Antigens
  • MHC class II transactivator protein
  • Nuclear Proteins
  • Superantigens
  • Trans-Activators
  • tat Gene Products, Human Immunodeficiency Virus
  • enterotoxin D, Staphylococcal
  • Positive Transcriptional Elongation Factor B
  • Protein-Serine-Threonine Kinases
  • CDK9 protein, human
  • Cyclin-Dependent Kinase 9
  • Cyclin-Dependent Kinases