High degree of idiotypic cross-reactivity among murine monoclonal antibodies to thyroglobulin.

The idiotypy of five mouse monoclonal antibodies (mAb) generated against human thyroglobulin (Tg) and reacting with Tg from various species, including murine Tg, was investigated. Rabbit antisera made specific for the idiotype (Id) of three mAb (62, 1.15, and 9.1) were used. By competitive inhibition of homologous Id-anti-Id binding, a surprisingly high degree of Id cross-reactivity was found. The Id determinants on mAb appeared located in or close to the paratope because anti-Id could inhibit their binding to Tg in each instance. Interestingly enough, no true "private" Id could be identified. Id cross-reactivity was found between mAb generated in different fusion experiments and recognizing apparently distinct epitopes on Tg. These results suggest that the immune response to phylogenetically highly conserved epitopes on antigen of internal origin, such as Tg, is idiotypically restricted.