Use of anti-idiotypic antibodies as cell-surface receptor probes

Abstract

Anti-idiotypic antibodies have been raised against antibodies to retinol-binding protein (RBP) and to insulin. After absorption the anti-idiotypic antibodies recognized the antigen-combining sites of the antibodies used as the immunogen but of no other antibodies. Some of the anti-idiotypic antibodies raised against antibodies to RBP bound specificanly to rat intestine epithelial cells, which have a physiological cell-surface receptor for RBP. The RBP receptor mediates the uptake of retinol from RBP to the cells. This uptake was abolished in a concentration-dependent manner by the anti-idiotypic antibodies, which obviously competed with RBP for binding to the receptor.Anti-idiotypic antibodies against antibodies to insulin inhibited the binding of "25I-labeled insulin to isolated rat epididymal fat cells, whereas anti-idiotypic antibodies raised against antibodies to RBP had no effect. Furthermore, on interacting with young rat thymocytes, anti-idiotypic antibodies against antibodies to insulin stimulated the uptake by the cells of aaminoisobutyric acid, thereby mimicking the effect of insulin.These results suggest that in some cases anti-idiotypic antibodies may be useful tools in elucidating structure-function relationships for cell-membrane receptors. The immune system recognizes foreign substances by generation of antibodies that display an almost endless variety of combining sites. Thus, even a small, chemically well-defined molecule may, on immunization, give rise to stimulation of about 100 antibody-forming clones. Each clone produces a specific antibody with a unique amino acid sequence in the variable region (1). Due to the enormous variability in the antibody population, it seemed possible that among all the different antibodies that are elicited as a result of the immunization with, e.g., a hormone, a few antibodies might recognize that hormone in a fashion that mimics the way a physiological receptor recognizes the hormone. If so, the combining sites of such receptor-like antibodies might display structural features in common with the hormone-binding part of the receptor. Consequently, a few of a second set of antibodies raised against the combining sites, the idiotopes, of the "receptor-like" antibodies may, in their variable portions, be similar to those structures of the hormone that bind to the physiological receptor. Among such second sets of antibodies, anti-idiotypic antibodies, some would presumably interact with the hormone receptor in a hormone-like fashion.To test the above reasoning we have raised anti-idiotypic antibodies against antibodies to retinol-binding protein (RBP) and to insulin. Since cell-surface receptors for RBP (2) and insulin (for a review, see ref. 3) exist, the possible binding of the anti-idiotypic antibodies to these receptors has been explored. This communication presents data that demonstrate that such anti-idiotypic antibodies may become useful tools in elucidating the structure and function of cell-surface receptors.The costs of publication of this article...

Sequestrin, a CD36 recognition protein on Plasmodium falciparum malaria-infected erythrocytes identified by anti-idiotype antibodies.

“…Anti-Id antibodies raised against the antigen binding sites of antibodies specific for receptors have been used as cellsurface probes to define the molecular interactions between ligands and receptors (8). Some anti-Id antibodies contain the internal image of the receptor (Ab2) and may recognize a complementary receptor-binding site.…”

Rabbits immunized with thyroid-stimulating hormone produce autoantiidiotypic thyroid-stimulating antibodies.

“…Thus, antibodies to antiinsulin, antiformyl peptides, and antialprenolol have been found to have agonist activities in appropriate bioassays (4)(5)(6)(7). These findings suggest an alternate mode of autoimmunization as the source of TSI.…”

“…At 160 d, two out of six animals immunized with hTSH, two out of six immunized with hTSH,3, and two out of the four surviving animals immunized with bTSH had TSI activities of 6-18 ,uU TSH eq. These values were >2 SD above the mean of the hSAimmunized animals, 4 (Fig. 2).…”

New dimensions in vaccinology: A new insight

“…Based on the ability of the anti-idiotypes to mimic foreign antigens, these have found use as alternatives to conventional vaccines in inducing anti-parasitic, antiviral, anti-bacterial immunity (75). They have been particularly effective in the following case:…”