Open AccessAnti-immune complex antibodies enhance affinity and specificity of primary antibodies.
Author(s) -
Edwin F. Ullman,
Gary L. Milburn,
John G. Jelesko,
Kesavan Radika,
Marcel R. Pirio,
Thomas Kempe,
Carl N. Skold
Publication year - 1993
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.90.4.1184
Subject(s) - immunogen , antibody , epitope , immune complex , chemistry , antigen , immune system , binding site , paratope , blocking antibody , antigen antibody complex , immunoglobulin idiotypes , idiotype , monoclonal antibody , microbiology and biotechnology , biology , biochemistry , immunology
Antibodies have previously been described that enhance the binding of a second antibody to its antigen. The origin of this effect has been variously ascribed to binding to a neodeterminant on the Fc region, to a combined determinant representing portions of the second antibody and the immunogen, and to a ligand-induced conformation of the Fab fragment. This paper describes an antibody that recognizes an immune complex of an antibody to tetrahydrocannabinol (THC). The antibody binds the anti-THC antibody at an epitope recognized by an anti-idiotype antibody that is capable of blocking THC binding. The ability of various THC derivatives to enhance or inhibit binding taken together with equilibria and kinetic data support a model in which the anti-immune complex antibody interacts through adventitious binding to pendant groups on the THC derivatives. This type of interaction offers the opportunity to increase the sensitivity and specificity of immunoassays beyond the limits imposed by normal antibody binding. The implications of these findings with regard to earlier observations of anti-immune complex antibodies are discussed.