Complementation cloning of an MHC class II transactivator mutated in hereditary MHC class II deficiency (or bare lymphocyte syndrome)

Cell. 1993 Oct 8;75(1):135-46.


Hereditary major histocompatibility complex (MHC) class II deficiency (or bare lymphocyte syndrome) is a form of severe primary immunodeficiency with a total lack of MHC class II expression. It is due to a defect in the regulation of MHC class II genes. A novel gene was isolated by complementation cloning, using an MHC class II-negative mutant cell line. This gene (CIITA) functions as a transactivator of MHC class II gene expression and restores expression of all MHC class II isotypes in mutant cells. In addition, CIITA fully corrects the MHC class II regulatory defect of cells from patients with bare lymphocyte syndrome. In this disease we have identified a splicing mutation that results in a 24 amino acid deletion in CIITA, resulting in loss of function of the transactivator. Hence, the CIITA gene is essential for MHC class II gene expression and has been shown to be responsible for hereditary MHC class II deficiency.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Base Sequence
  • Cell Line
  • Cloning, Molecular
  • DNA, Complementary / isolation & purification
  • DNA, Complementary / metabolism
  • Exons
  • Gene Expression Regulation / immunology*
  • Genes, MHC Class II / genetics*
  • Genes, Regulator*
  • Genetic Complementation Test
  • HLA-D Antigens / genetics*
  • Humans
  • Immunologic Deficiency Syndromes / genetics*
  • Immunologic Deficiency Syndromes / immunology
  • Lymphocytes / immunology
  • Molecular Sequence Data
  • Mutagenesis, Insertional
  • Nuclear Proteins*
  • Oligodeoxyribonucleotides
  • RNA Splicing
  • Sequence Deletion*
  • Trans-Activators / biosynthesis
  • Trans-Activators / genetics*
  • Transfection
  • Tumor Cells, Cultured


  • DNA, Complementary
  • HLA-D Antigens
  • MHC class II transactivator protein
  • Nuclear Proteins
  • Oligodeoxyribonucleotides
  • Trans-Activators

Associated data

  • GENBANK/L20823
  • GENBANK/L20888
  • GENBANK/L20889
  • GENBANK/L33709
  • GENBANK/S60904
  • GENBANK/S60905
  • GENBANK/S60924
  • GENBANK/S68033
  • GENBANK/S68036
  • GENBANK/X74301