Five groups of antigenic determinants on DNA identified by monoclonal antibodies from (NZB X NZW)F1 and MRL/Mp-lpr/lpr mice.

A library of monoclonal antibodies (MCA) reactive with DNA was derived from mice with lupus-like disease. The combining reactions of the antibodies was determined by ELISA, precipitation assay and indirect immunofluorescence assay on cells. On the basis of their reactions in these assays, the MCA have been classified into five taxonomic groups. MCA in Group I react with conformational determinants on double-stranded DNA (dsDNA); those in Group II with conformational backbone-dependent sugar-phosphate determinants on dsDNA and single-stranded DNA (ssDNA); those in Group III with determinants predominantly expressed on ssDNA; those in Group IV with base-dependent determinants on ssDNA, and those in Group V with determinants on both DNA and RNA. It is concluded that antibodies which react with DNA are collectively of limited heterogeneity with regard to their specificity. The study illustrates how, upon traditional interpretation, different assay systems may give discordant results in the assignment of specificity to antibodies reactive with DNA.