Antigenic structure of DNA: relatively high inhibitory activity of di- and trideoxyribonucleotide derived from DNase digest on the interaction of thermally denatured DNA with systemic lupus erythematosus sera

Abstract

The antigenic determinant of thermally denatured DNA reactive with systemic lupus erythematosus (SLE) sera was examined by hapten inhibition assay. We used oligonucleotides with different chain lengths (2-8) derived from DNase I digests of salmon sperm DNA in Farr's radioimmunoassay with thermally denatured mouse embryo 3H-DNA as antigen, and the effect of dextran sulphate addition to the assay mixture on the inhibitory activity of oligonucleotides was examined. A characteristic oligonucleotide inhibition pattern on DNA binding by SLE sera was observed in the assay system without dextran sulphate. Di-and/or trinucleotide inhibited the binding more effectively than tetra-and/or pentanucleotide. These patterns were also observed in DNA-normal serum interaction. When dextran sulphate was added to the mixture, the inhibition pattern changed; the inhibitory activity of oligonucleotides increased with chain length in both serum groups. The inhibitory potency of di- and trinucleotide was higher on DNA-SLE sera than on DNA-normal sera interaction. The high potency of short-chain oligomers in SLE sera is obviously different from that in experimentally elicited anti-DNA sera suggesting that different mechanism(s) are involved in antibody production in normal individuals and SLE patients.