R.S. Accolla

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 deoxyribonucleic acid (dsDNA) have been recently demonstrated in peripheral blood mononuclear cells of patients with systemic lupus erythematosus. Their activation 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 oligonucleotides, dsDNA was detected on the cell membrane and in the lysates of HLA‐II+ but not of isogenic HLA‐II− cell lines. We demonstrate that dsDNA binding inhibits that of a specific peptide to HLA‐II. Mixed lymphocyte reaction and antigen‐specific T cell proliferation were inhibited by the preincubation of stimulator cells or antigen‐presenting cells with dsDNA. These results suggest 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 “n;‐occupied” by dsDNA.