Individuals with systemic autoimmune diseases develop autoantibodies t
o nucleosome antigens. For many years, investigators have devoted much
effort to precisely mapping epitopes on individual chromatin componen
ts. This approach, however, overlooks the existence of determinants th
at result from multimolecular interactions among nucleosome elements,
such as DNA and histones. Anti-nucleosome antibodies can recognize a v
ariety of complex epitopes and are especially prevalent in spontaneous
and drug-induced lupus. Using numerous monoclonal anti-nucleosome ant
ibodies obtained from autoimmune mice, we have further characterized t
hese determinants and sequenced the variable region genes of these aut
oantibodies. I herein review these studies and their implications for
the origin of antinuclear autoantibodies. (C) 1997 Academic Press, Inc
.