Defective MHC class II expression in an MHC class II deficiency patient iscaused by a novel deletion of a splice donor site in the MHC class II transactivator gene

MHC class II deficiency patients are mutated for transcription factors that regulate the expression of major histocompatibility complex (MHC) class II genes. Four complementation groups (A-D) are defined and the gene defectiv e in group A has been shown to encode the MHC class II transactivator (CIIT A). Here, we report the molecular characterization of a new MHC class II de ficiency patient, ATU, Cell fusion experiments indicated that ATU belongs t o complementation group A. Subsequent mutation analysis revealed that the C IITA mRNA lacked 84 nucleotides, This deletion was the result of the absenc e of a splice donor site in the CIITA gene of ATU. As a result of this nove l homozygous genomic deletion, ATU CIITA failed to transactivate MHC class II genes. Furthermore, this truncated CIITA of ATU did not display a domina nt negative effect on CIITA-mediated transactivation of various isotypic MH C class II promoters.