Double-stranded deoxyribonucleic acid binds to HLA class II molecules and inhibits HLA class II-mediated antigen presentation

CD4(+) T cells proliferating in response to purified double-stranded deoxyr ibonucleic acid (dsDNA) have been recently demonstrated in peripheral blood mononuclear cells of patients with systemic lupus erythematosus. Their act ivation was inhibited by anti-HLA class II (HLA-II) monoclonal antibodies; thus, the existence of a molecular interaction between dsDNA and HLA-II is conceivable. In this report we show that dsDNA specifically bind to HLA-II. After preincubating cells with purified dsDNA or synthetic oligonucleotide s, dsDNA was detected on the cell membrane and in the lysates of HLA-II+ bu t not of isogenic HLA-II- cell lines. We demonstrate that dsDNA binding inh ibits that of a specific peptide to HLA-II. Mixed lymphocyte reaction and a ntigen-specific T cell proliferation were inhibited by the preincubation of stimulator cells or antigen-presenting cells with dsDNA. These results sug gest the existence of a novel mechanism of down-modulation of the CD4(+) T cell function generated by lack of stimulation due to the HLA-II presenting molecules being "occupied" by dsDNA.