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 pr esence of conserved sequence motifs called S,X and Y boxes, which are crucial for regulation of transcription of these genes. In humans, pro moter polymorphism is known to result in differential transcriptional activity at both inter-locus and inter-allelic levels, but it is not y et known how this relates to tissue-specific expression of MHC class I I 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 al lelic polymorphisms which were mainly confined to the X box. The promo ter 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 a llele- and tissue-specific activity patterns. Mutagenesis experiments in which the X(2) box was reshuffled between I-A beta alleles demonstr ated that this box contributes to regulation of differential MHC class II expression in the four cell types. The possibility is discussed th at tissue-specific MHC class II expression may control differentiation of T-cell subsets.