A viral DNA-binding domain elicits anti-DNA antibodies of different specificities

We have previously demonstrated that immunization of normal mice with a defined protein:DNA complex comprising the C-terminal DNA-binding domain of the human papillomavirus E2 protein and its cognate site 35 oligonucleotide, results in high antibody titers against both E2 and its target DNA sequence. Here we show that repeated immunization with the isolated form of the E2 domain also elicits anti-DNA antibodies, but in this case, no preferential binding for a given sequence was observed, indicating that these antibodies have broad specificity for DNA. Taken together our results indicate that this viral protein can induce two classes of anti-DNA antibody responses: one directed against endogenous DNA and other in which anti-site 35-specific antibodies are produced. In both cases, the character of the resulting anti-DNA response seems to be directed by the DNA molecule that the protein binds in vivo. Evaluation of the fine specificity of the antibodies induced by the free and bound states of this single foreign DNA-binding protein would contribute to the understanding of the processes involved in the acquisition of particular DNA specificities by anti-DNA antibodies.