Discoordinate expression of invariant chain and MHC class II genes in class II transactivator-transfected fibroblasts defective for RFX5.
MHC class II deficiency or bare lymphocyte syndrome is a severe combined immunodeficiency caused by defects in MHC-specific transcription factors. In the present study, we show that fibroblasts derived from a recently identified bare lymphocyte syndrome patient, SSI, were mutated for RFX5, one of the DNA-binding components of the RFX complex. Despite the lack of functional RFX5 and resulting MHC class II-deficient phenotype, transfection of exogenous class II transactivator (CIITA) in these fibroblasts can overcome this defect, resulting in the expression of HLA-DR, but not of DP, DQ, and invariant chain. The lack of invariant chain expression correlated with lack of CIITA-mediated transactivation of the invariant chain promoter in transient transfection assays in SSI fibroblast cells. Consequently, these CIITA transfectants lacked Ag-presenting functions.
Peijnenburg
A
A
Department of Immunohematology and Blood Bank, Leiden University Medical Center, The Netherlands.
Van Eggermond
M J
MJ
Gobin
S J
SJ
Van den Berg
R
R
Godthelp
B C
BC
Vossen
J M
JM
Van den Elsen
P J
PJ
D000483:Alleles; D000944:Antigens, Differentiation, B-Lymphocyte / Q000096:biosynthesis*; D002459:Cell Fusion / Q000235:genetics; D002462:Cell Membrane / Q000276:immunology / Q000378:metabolism; D018388:Codon, Terminator / Q000235:genetics; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics*; D005260:Female; D005347:Fibroblasts / Q000276:immunology / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000276:immunology*; D005802:Genes, MHC Class II; D005816:Genetic Complementation Test; D006684:HLA-DR Antigens / Q000096:biosynthesis; D000949:Histocompatibility Antigens Class II / Q000096:biosynthesis*; D006801:Humans; D008297:Male; D009687:Nuclear Proteins; D017354:Point Mutation / Q000276:immunology; D000071701:Regulatory Factor X Transcription Factors; D016511:Severe Combined Immunodeficiency / Q000235:genetics / Q000276:immunology; D015534:Trans-Activators / Q000235:genetics*; D014162:Transfection / Q000276:immunology
D000944:Antigens, Differentiation, B-Lymphocyte; D018388:Codon, Terminator; D004268:DNA-Binding Proteins; D006684:HLA-DR Antigens; D000949:Histocompatibility Antigens Class II; C083728:MHC class II transactivator protein; D009687:Nuclear Proteins; C093524:RFX5 protein, human; D000071701:Regulatory Factor X Transcription Factors; D015534:Trans-Activators; C045084:invariant chain