Determination of the molecular mechanisms influencing HLA-DRB gene exp
ression would allow better understanding of the regulation of the immu
ne response in normal as well as in pathological conditions. We starte
d an extensive sequencing analysis of the proximal promoter regions of
the DRB genes and observed a nucleotide polymorphism involving the cl
assical regulatory regions of the DRB promoters. These nucleotide subs
titutions were observed to induce variations of the promoter activitie
s as assessed by chloramphenicol acetyl transferase assays and the qua
ntification of DRB transcripts. Similar analysis performed in patients
with rheumatoid arthritis strongly suggests dysregulation of HLA-DRB
gene expression.