Polymorphic MHC class II promoters exhibit distinct expression pattern in various antigen-presenting cell lines.
The promoter regions of MHC class II genes are characterized by the presence of conserved sequence motifs called S,X and Y boxes, which are crucial for regulation of transcription of these genes. In humans, promoter polymorphism is known to result in differential transcriptional activity at both inter-locus and inter-allelic levels, but it is not yet known how this relates to tissue-specific expression of MHC class II molecules. We sequenced the 5' regulatory regions of alpha and beta genes of I-A and I-E molecules from four mouse haplotypes and found allelic polymorphisms which were mainly confined to the X box. The promoter sequences of I-Ea genes were non-polymorphic. Transfection of four antigen-presenting cell types with promoter-reporter gene constructs revealed that the promoter sequence polymorphisms result in distinct allele- and tissue-specific activity patterns. Mutagenesis experiments in which the X2 box was reshuffled between I-A beta alleles demonstrated that this box contributes to regulation of differential MHC class II expression in the four cell types. The possibility is discussed that tissue-specific MHC class II expression may control differentiation of T-cell subsets.
Janitz
M
M
Deutsches RheumaForschungsZentrum, Berlin, Germany.
Mitchison
A
A
Reiners-Schramm
L
L
Lauster
R
R
D000818:Animals; D000938:Antigen-Presenting Cells; D001483:Base Sequence; D004247:DNA; D005786:Gene Expression Regulation; D005802:Genes, MHC Class II; D051379:Mice; D008969:Molecular Sequence Data; D016296:Mutagenesis; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D017422:Sequence Analysis, DNA; D014407:Tumor Cells, Cultured
D004247:DNA