Anti-idiotypic antibodies: implications of internal image-based vaccines for infectious diseases.

Abstract

An idiotype or idiotypic determinant (Id) defines the variable (V) region of the antibody molecule. Originally proposed by Oudin [1] to designate antigenic determinants that are unique to a small set of antibody molecules, Ids have often served as genetic markers for the V region. Initially, antisera were generated against homogeneous immunoglobulins such as myelomas or Bence-Jones proteins and, after appropriate adsorptions, these antisera reacted only with the myeloma protein used as the immunogen and not with other myelomas or conventional antibodies. The first reports of this antigenic individuality [2, 3] were based upon a study of human myeloma proteins, and these studies were extended to report on a series of conventional antibodies in humans and rabbits [1, 4]. In these early studies, the term Id was used to convey a unique antigen present on an immunoglobulin molecule, and this unique specificity was detected by antiidiotypic reagents. However, in numerous instances it has been demonstrated that antibodies to a given antigen may share Id, as determined by the reaction of reagents with an anti-idiotype. Private Id are restricted to a single immunoglobulin molecule, whereas or cross-reactive Id are shared by more than one antibody. It is the public or shared Id that are useful as V-region phenotypic markers and most likely represent germ-line gene products. The V region of the antibody contains within its structure the antigen-binding site. The specific region that makes contact with the antigen is referred to as the paratope. A site on the surface of a single antibody molecule that can induce antibody production and is recognized by anti-idiotypic reagents is r ferred to as an idiotope. The idiotypic determinant (Id) is then a collection of different idiotopes. One must remember that the antigen is defined by an antibody as an Id is defined by anti-idiotypic antiserum (anti-Id). It is the complementary nature of the conformation or three-dimensional structure of the antigen to the structure or conformation of the paratope that generates a sufficiently attractive force for antigen-antibody binding to occur. The threedimensional fit between antigen and antibody should also occur between the Id and anti-Id in order for the binding reaction to take place. Thus, there is complementarity between the Id and anti-Id that allows this specific binding to occur. It is of note that the paratope may or may not be the same site as that recognized by the anti-Id. Therefore, an Id can be associated with a defined conformation or region with the V-region that is not involved in the binding site of antigen.