Idiotypes

Geha R, Quinti I, Austen K, Cicardi M, Sheffer A, Rosen F Acquired Cl-inhibitor deficiency associated with anti-idiotypic antibody to monoclonal immunoglobuhns. N Engl J Med 1985 312 534-540. Donaldson V, Hess E, McAdams A Lupus-erythe-matosus-like disease in three umelated women with hereditary angioneurotic edema. Arm Intern Med 1977 86 312-313. 

Antibody feedback. Antibodies produced in response to an antigen are capable of inhibiting further immune responses to that antigen. This may occur due to diminishing antigen levels as a result of its combination with antibody or through an idiotypic network. 

Idiotypic network. Idiotypic determinants (idiotypes) are unique antigenic epitopes characteristic of the antigen receptors on the surface of T and B cells. They are associated with the variable regions of these receptors. Antibodies produced by B cells as the result of antigenic stimulation can themselves stimulate the production of auto-anti-idiotypic antibodies which have the ability to combine with the B-cell receptor (Ig) and thus can dampen down the immune response. Idiotypes may likewise stimulate the production of T cells specific for idiotypic determinants. Jerne (1974) postulated his... 

Ab2 S Anti-idiotype antibody which binds to the antigen binding region Ab3 Anti-anti-idiotype antibody Abcc Antibody dependent cellular cytotoxicity... 

CRI Cross-reactive idiotype CRPC- reactive protein eSA Cyclosporin A CSF Colony-stimulating factor... 

Hypersensitivity to foreign epitopes Anti-idiotypic response to normal cells Immune complex disease Potential MPS toxicity D. Specific specificity... 

Garcia, K.C., Ronco, P.M., Verroust, P.J., Briinger, AT. and Mazel, L.M. (1992) Three-dimensional structure of an angiotensin II-Fab complex at 3 A hormone recognition by an anti-idiotypic antibody, Science, 257, 502-507. 

Swanson, S.J., Lin, B.-F., Mullenix, M.C., and Mortensen, R.F. (1991) A synthetic peptide corresponding to the phosphorylcholine (PC)-binding region of human C-reactive protein possesses the TEPC-15 myeloma PC-idiotype. J. Immunol. 146, 1596-1601. 

Szabo, J., Kruger, S.R., and Beall, G.N. (1989) Detection of cells producing anti-idiotypic antibody to thyroid stimulating hormone-reactive antibodies. Immunol. Invest. 18, 879-884. 

Teale, J.M., and Kearney, J.R. (1986) Clonotypic analysis of the fetal B cell repertoire Evidence for an early and predominant expression of idiotypes associated with the VH 36-60 family. J. Mol. Cell. Immunol. 2, 283-292. 

Levitsky, H.I. et al., Immunization with granulocyte-macrophage colony-stimulating factor- transduced, but not B7-l-transduced, lymphoma cells primes idiotype-specific T cells and generates potent systemic antitumor immunity, J Immunol, 156, 3858, 1996. 

Mercuric chloride in the BN rat gives a lymphoproliferation in spleen and lymph nodes, including B and T helper cells, an increase in the number of Ig containing cells resulting in a rise in all serum Ig isotypes and an early thymic atrophy [196]. The kinetics of the increase in the serum level of various Ig isotypes were similar to that observed for IgE, suggesting spontaneous autoregulation, which could involve suppressor T cells [ 197, 198] and/or auto-anti-idiotypic antibodies [ 199]. 

Monoclonal antibody (or component) Hybridoma human cell line Probably predictable anitgenicity Moderate Anti-tumor antibody for imaging anti-idiotype antibody as vaccine... 

There is also considered to be a population of T suppressor cells which acts to down-regulate both T helper cells and B cells, whether through antigen-specific or idiotype-specific mechanisms. The epitopes on the lymphocyte receptor (id-iotype) recognized by the receptor on another lymphocyte (anti-idotype) can form a network of interactions through which suppression may be mediated. 

Igarashi, K., Kaneda, M., Yamaji, A., Saido, T.C., Kikkawa, U., Qno, Y., Inoue, K., and Umeda, M., 1995, A novel phosphatidylserine-binding peptide motif defined by an anti-idiotypic monoclonal antibody. Localization of phosphatidylserine-specific binding sites on protein kinase C and phosphatidylserine decarboxylase. J. Biol. Chem. 270 29075-29078. 

Wetterwald A, Skvaril F, Muller U, Blaser K Isotypic and idiotypic characterization of anti-bee venom phospholipase A2 antibodies. Arch Allergy Appl Immunol 1985 77 195-197. 

Figure 26 Production of abzymes using the anti-idiotypic antibodies method.

The most outstanding example illustrating this strategy came from the team of Alain Friboulet and Daniel Thomas, who produced anti-idiotype antibodies against a monoclonal antibody AE2 that was a competitive inhibitor of acetylcholine esterase. One of the selected antibodies, 9A8, catalyzes the hydrolysis of acetylthio-choline with a pseudo first-order rate constant /feat = 81 and a factor of acceleration of 4.2 x 10 . These remarkable parameters, which are only two orders of magnitude lower when compared to those of the enzyme, make abzyme 9A8 the most powerful abzyme known until now. 

Immunogenicity Low titers of anti-idiotype antibodies to daclizumab were detected in the adult patients treated with daclizumab with an overall incidence of 14%. The incidence of anti-daclizumab antibodies observed in the pediatric patients was 34%. No antibodies that affected efficacy, safety, serum daclizumab levels or any other clinically related parameter were detected. 

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