Differential expression of HLA-DRB genes according to the polymorphism of their regulatory region.

The polymorphism of the HLA-class II molecules is directly involved in the specificity of the antigen presentation. We have previously described an allelic polymorphism in the proximal promoter region of the HLA-DRB genes. In this study, we demonstrate that this polymorphism has functional consequences on the transcriptional activity of the promoter of the different DRB genes. Indeed, transiently transfected DRB gene promoters into human B cell lines showed a marked difference in their ability to induce transcription of the chloramphenicol acetyl transferase (CAT) reporter gene. These findings suggest the presence of two interdependent effects of the HLA-class II molecules on the specificity of the immune response: one corresponding to the allelic polymorphism of the peptide-binding site and the second resulting from the polymorphism of the promoter regions inducing a variable expression of the DRB genes.