ANTI-METATYPE ANTIBODIES IN IMMUNOASSAYS

In this review anti-metatype antibodies are described invoking new pri nciples in immunoassay development. Anti-metatype antibodies are immun ological reagents specific for the conformation of the liganded antibo dy active site which do not interact with bound ligand or unliganded a ntibody. Relationships between anti-metatype antibody reactivity and t he ligand-induced conformational state of monoclonal antibodies are re viewed with emphasis on the fluorescein hapten as a small molecule mod el system. One characteristic result of the interaction of anti-metaty pe antibodies with liganded antibodies is a significant delay in the d issociation rate (k(2)) of the ligand bound within the primary immune complex. The latter is an important consideration for assay developmen t. Polyclonal and monoclonal anti-metatype antibody reagents are chara cterized in terms of their differential effects on the ligand dissocia tion rate. Anti-metatype antibody reactivity is further discussed in t erms of protein-protein specificity patterns and relative interactions with idiotype-family members, structural derivatives, and site-specif ic mutants. Incorporation of principles inherent in the anti-metatype concept and their application to assay development are summarized.