Structural and functional analysis of HLA-DR beta-promoter polymorphism and isomorphism.

Evolutionary relatedness among the highly polymorphic DR beta genes has been established based on shared nucleotide sequences and structural organization of DR beta loci. The evolution of promoter regions of the B10701, B10101, B11501, B50101 genes was analyzed by cloning and sequencing. This shows that the polymorphism and isomorphism of HLA DR beta genes extend into the 5' flanking promoter region of the genes and that evolutionary relatedness also exists among the DR beta gene promoters. This suggests that DR beta gene promoters and coding regions coevolved. The effect of the naturally occurring nucleotide substitutions in the polymorphic and isomorphic DR beta promoters on transcriptional activity has been determined in a transient expression system. The transcriptional activity of two polymorphic DR beta promoters, B11501 and B10701, and two isomorphic DR2 promoters, B11501 and B50101, is the same for these promoters. Together these data suggest that naturally occurring substitutions do not significantly affect the transcriptional activity of these promoters.