Maturation of Immune Response to Insulin: Recruitment of New Epitopes by Antibodies

Guinea pigs were immunized with regular insulin in Freund9s adjuvant weekly ( N = 6) or with NPH insulin daily ( N = 10). The concentrations, the affinities, and the sizes of the insulin-immunoglobin G (IgG) antibody complexes were determined by ultracentrifugation. During the immune response to insulin, 7-S complexes were observed after 3 wk, and 10-S complexes were observed after 4 wk (2 P P N = 6) and in inbred strain II l.b.m. guinea pigs (2 P N = 7). Insulin may act as a monovalent antigen (7 S) after 3 wk and become bivalent after 4 wk (10 S). The change in valency is enhanced by antibody transfer. It reflects the formation of antibodies recognizing new epitopes on insulin.