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 HL4-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 'occupied' by dsDNA.
|Number of pages||12|
|Journal||European Journal of Immunology|
|Publication status||Published - Dec 1998|
- Antigen presentation
- HLA class II molecule
- Mixed leukocyte reaction
ASJC Scopus subject areas