title: Defective MHC class II expression in an MHC class II deficiency patient is caused by a novel deletion of a splice donor site in the MHC class II transactivator gene.
abstract: 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 defective in group A has been shown to encode the MHC class II transactivator (CIITA). Here, we report the molecular characterization of a new MHC class II deficiency patient, ATU. Cell fusion experiments indicated that ATU belongs to complementation group A. Subsequent mutation analysis revealed that the CIITA mRNA lacked 84 nucleotides. This deletion was the result of the absence of a splice donor site in the CIITA gene of ATU. As a result of this novel homozygous genomic deletion, ATU CIITA failed to transactivate MHC class II genes. Furthermore, this truncated CIITA of ATU did not display a dominant negative effect on CIITA-mediated transactivation of various isotypic MHC class II promoters.
authors.affiliation: Department of Immunohematology and Blood Bank, Leiden University Medical Center, Building 1, E3-Q, P.O. Box 9600, 2300 RC Leiden, The Netherlands.
authors.forename: A
authors.initials: A
authors.lastname: Peijnenburg
authors.forename: R
authors.initials: R
authors.lastname: Van den Berg
authors.forename: M J
authors.initials: MJ
authors.lastname: Van Eggermond
authors.forename: O
authors.initials: O
authors.lastname: Sanal
authors.forename: J M
authors.initials: JM
authors.lastname: Vossen
authors.forename: A M
authors.initials: AM
authors.lastname: Lennon
authors.forename: C
authors.initials: C
authors.lastname: Alcaïde-Loridan
authors.forename: P J
authors.initials: PJ
authors.lastname: Van den Elsen
mesh_terms: D000944:Antigens, Differentiation, B-Lymphocyte / Q000235:genetics; D001483:Base Sequence; D002459:Cell Fusion; D002461:Cell Line, Transformed; D005091:Exons / Q000235:genetics; D005347:Fibroblasts; D015870:Gene Expression / Q000187:drug effects / Q000235:genetics*; D005805:Genes, MHC Class I / Q000235:genetics; D005802:Genes, MHC Class II / Q000235:genetics* / Q000276:immunology; D005816:Genetic Complementation Test; D000949:Histocompatibility Antigens Class II / Q000235:genetics; D006720:Homozygote; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D007930:Leucine / Q000235:genetics; D009687:Nuclear Proteins; D010641:Phenotype; D011401:Promoter Regions, Genetic / Q000235:genetics; D012326:RNA Splicing / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017384:Sequence Deletion / Q000235:genetics*; D015534:Trans-Activators / Q000737:chemistry / Q000235:genetics*; D015533:Transcriptional Activation / Q000187:drug effects / Q000235:genetics; D001613:beta 2-Microglobulin / Q000235:genetics
chemical_list: D000944:Antigens, Differentiation, B-Lymphocyte; D000949:Histocompatibility Antigens Class II; C083728:MHC class II transactivator protein; D009687:Nuclear Proteins; D012333:RNA, Messenger; D015534:Trans-Activators; D001613:beta 2-Microglobulin; C045084:invariant chain; D007371:Interferon-gamma; D007930:Leucine