Abstract
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.
Publication types
-
Case Reports
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Alleles
-
Antigens, Differentiation, B-Lymphocyte / biosynthesis*
-
Cell Fusion / genetics
-
Cell Membrane / immunology
-
Cell Membrane / metabolism
-
Codon, Terminator / genetics
-
DNA-Binding Proteins / biosynthesis
-
DNA-Binding Proteins / genetics*
-
Female
-
Fibroblasts / immunology
-
Fibroblasts / metabolism*
-
Gene Expression Regulation / immunology*
-
Genes, MHC Class II*
-
Genetic Complementation Test
-
HLA-DR Antigens / biosynthesis
-
Histocompatibility Antigens Class II / biosynthesis*
-
Humans
-
Male
-
Nuclear Proteins*
-
Point Mutation / immunology
-
Regulatory Factor X Transcription Factors
-
Severe Combined Immunodeficiency / genetics
-
Severe Combined Immunodeficiency / immunology
-
Trans-Activators / genetics*
-
Transfection / immunology
Substances
-
Antigens, Differentiation, B-Lymphocyte
-
Codon, Terminator
-
DNA-Binding Proteins
-
HLA-DR Antigens
-
Histocompatibility Antigens Class II
-
MHC class II transactivator protein
-
Nuclear Proteins
-
RFX5 protein, human
-
Regulatory Factor X Transcription Factors
-
Trans-Activators
-
invariant chain