Characterization of homologous anti-alpha-fetoprotein antibodies produced in rabbits.

The natural tolerance to alpha-fetoprotein (AFP) was broken in rabbits by immunizations with purified AFP from different species and homologous AFP chemically modified by haptenation. Some of the rabbits were boostered with rabbit AFP. The highest titers were obtained with human AFP, which shows a strong cross-reaction with rabbit AFP. The homologous antibodies were of lower avidity than heterologous (sheep) antisera. Injections with rabbit AFP did not alter the avidity or titer. All antibodies produced by injections with human AFP could be absorbed with the original immunogen, and no reactivity against determinants unique to rabbit AFP could be found. These results indicate that the antibody activity against autologous AFP is based on cross-reactivity and that the immunizations did not make the autologous AFP immunogenic. These findings may be important in view of the possible use of AFP as a target antigen in tumor immunotherapy.