Related Experiment Videos
Idiotype network responses to murine immunoglobulin G3 anti-carbohydrate antibodies
1Department of Cellular Immunology, IDEC Pharmaceuticals Corporation, La Jolla, California 92037.
Two murine monoclonal antibodies, 8A6 and 8C2, were generated against the carbohydrate moiety of tumor-associated disialoganglioside. Both of the antibodies were of the immunoglobulin G3 (IgG3), K isotype subclass. One of these antibodies (8A6) was used as a network immunogen for the generation of anti-idiotype antibodies. Two AB2 anti-idiotype antibodies were identified. One AB2 (12E5) was subsequently shown to recognize a linear epitope of the 8A6 kappa light chain. The second AB2 (9H8), recognizes a conformational epitope which is dependent on the maintenance of the tertiary structure of the idiotype. Both anti-idiotypes were injected into (syngeneic) mice and (xenogeneic) rabbits to evaluate their effectiveness as "network" antigens in promoting AB3 and anti-carbohydrate AB1' responses. AB3 populations from both syngeneic and xenogeneic hosts were found to be idiotype-specific, yet were unable to produce a measurable subpopulation of anti-tumor (AB1'). These studies suggest that IgG3 isotypes may not be suitable idiotype templates for the mimicry of carbohydrate epitopes.
Two murine monoclonal antibodies, 8A6 and 8C2, were generated against the carbohydrate moiety of tumor-associated disialoganglioside. Both of the antibodies were of the immunoglobulin G3 (IgG3), K isotype subclass. One of these antibodies (8A6) was used as a network immunogen for the generation of anti-idiotype antibodies. Two AB2 anti-idiotype antibodies were identified. One AB2 (12E5) was subsequently shown to recognize a linear epitope of the 8A6 kappa light chain. The second AB2 (9H8), recognizes a conformational epitope which is dependent on the maintenance of the tertiary structure of the idiotype. Both anti-idiotypes were injected into (syngeneic) mice and (xenogeneic) rabbits to evaluate their effectiveness as "network" antigens in promoting AB3 and anti-carbohydrate AB1' responses. AB3 populations from both syngeneic and xenogeneic hosts were found to be idiotype-specific, yet were unable to produce a measurable subpopulation of anti-tumor (AB1'). These studies suggest that IgG3 isotypes may not be suitable idiotype templates for the mimicry of carbohydrate epitopes.