Studies on the Immunogenicity of Antigen-Antibody Precipitates

Abstract

Summary Guinea pigs immunized with antibody excess immune precipitates of human γG globulin (HGG) and rabbit or guinea pig anti-Fab or anti-Fc antibody make little antibody to HGG. The small amount of anti-HGG antibody produced in each case was directed against antigenic determinants present in both the Fab and Fc portions of the HGG molecule, and thus bore no reflection on the specificity of the antibody in the complexes. This finding suggests that the suppression is to the whole antigen molecule rather than its individual antigenic determinants. The mechanism of the suppression of antibody formation to complexes comprised of immunogenic components cannot be explained in terms of antigenic competition for antibody-producing cells, nor in terms of “blocking” of antigenic determinants. It was shown that the combination of HGG with specific anti-Fab antibody at the equivalence point hinders only 21% of the Fc antigenic determinant, while in 4-fold antibody excess precipitates 66% of the Fc antigenic determinants are still capable of reacting with homologous antibody. Similarly, equivalence precipitates of HGG with anti-Fc antibody “block” only 16% of Fab determinants, whereas in 4-fold antibody excess precipitates 43% of the Fab determinants are “hidden.” Quantitatively, HGG bound in a 4-fold antibody excess precipitate with either anti-Fab or anti-Fc antibody has approximately 0.5% of the immunogenicity of the uncombined antigen. It thus appears that antigen in antibody excess immune precipitates is non-immunogenic, and that the antibody produced against HGG can be explained in terms of a 0.5% dissociation of the complex in vivo.