Anti-DNA antibodies are elevated in several autoimmune diseases, inclu
ding systemic lupus erythematosus, Yet, DNA was not shown to be presen
ted by molecules of the major histocompatibility complex (MHC), nor wa
s it reported to specifically stimulate T cells in vivo, although thes
e 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 immuniz
ed with a murine monoclonal anti-anti-DNA antibody, proliferated in re
sponse to DNA. Moreover, presentation of DNA by murine antigen-present
ing cells could be inhibited with an isotype-specific anti-Ia antibody
, and with peptides restricted by the same H-2 haplotype, suggesting t
hat it is MHC class II-mediated. These results indicate that DNA can p
lay a direct role in the regulation of T cells and in autoimmune proce
sses. (C) 1996 Academic Press, Inc.