MHC Class II-Mediated T Cell Response to DNA

Anti-DNA antibodies are elevated in several autoimmune diseases, including systemic lupus erythematosus. Yet, DNA was not shown to be presented by molecules of the major histocompatibility complex (MHC), nor was it reported to specifically stimulate T cellsin vivo,although these steps are essential for antibody production. We now demonstrate DNA-specific T cell activation, which involves presentation of DNA by MHC class II molecules. T cells, isolated from lymph nodes of mice immunized with a murine monoclonal anti-anti-DNA antibody, proliferated in response to DNA. Moreover, presentation of DNA by murine antigen-presenting cells could be inhibited with an isotype-specific anti-Ia antibody, and with peptides restricted by the same H-2 haplotype, suggesting that it is MHC class II-mediated. These results indicate that DNA can play a direct role in the regulation of T cells and in autoimmune processes.