Genetic Control of Combining Sites of Insulin Antibodies Produced by Guinea Pigs*,

Several reports (1-3) where large molecular weight natural-occurring antigens and markedly heterogeneous antigenic material were used have demonstrated a statistically significant relationship of genetic factors to the immune response. More recently Levine, Ojeda, and Benacerraf (4, 5) have been able to demonstrate a genetic control of the immune response of guinea pigs immunized with hapten-poly-L-lysine conjugates. Previous evidence (6) from this laboratory demonstrated that rabbits and guinea pigs produce insulin antibodies toward several determinants on the insulin molecule. The portions of the insulin molecule toward which antibodies were produced appeared to be an individual characteristic which varied from animal to animal. I t was therefore postulated that genetic factors controlled insulin antibody production. Supporting evidence (7) for genetic control of insulin antibody production demonstrated that inbred strain 2 guinea pigs produced antibodies to portions of beef insulin to which strain 13 guinea pigs could not produce antibodies. Additional supporting evidence that genetic factors control the configuration of the combining sites of insulin antibodies produced by guinea pigs is presented in this communication. Data consistent with the possibility that control of the antibody-combinlng site configuration may involve more than one gene and not multiple alleles at a given gene locus is also presented.