Several hybridomas reactive with nuclease and/or anti-idiotype have been produced and characterized. Syngenic anti-idiotypes have also been produced and are presently being characterized in both antibody and T cell systems. Competitive binding studies are used to determine epitopes of nuclease as defined by available monoclonal antibodies. Examination of the kinetics of inhibition of nuclease with combinations of monoclonal antibodies is being used to determine mechanism of inhibition of catalytic activity of this enzyme. Site-directed mutagenesis of the nuclease gene has provided numerous point mutants of nuclease which are being studied for changes in immune reactivity. Synthetic peptides of nuclease are being examined to determine the relative importance of specific sites for interacting with T cells and antibodies.