COMPLEMENTATION CLONING OF AN MHC CLASS-II TRANSACTIVATOR MUTATED IN HEREDITARY MHC CLASS-II DEFICIENCY (OR BARE LYMPHOCYTE SYNDROME)

Hereditary major histocompatibility complex (MHC) class II deficiency (or bare lymphocyte syndrome) is a form of severe primary immunodefici ency with a total lack of MHC class II expression. It is due to a defe ct 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 re gulatory 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 t he transactivator. Hence, the CIITA gene is essential for MHC class II gene expression and has been shown to be responsible for hereditary M HC class II deficiency.