Anti-idiotypic route to anti-acetylcholine receptor antibodies and experimental myasthenia gravis.

Abstract

tran.-3,3'-Bis[a-(trimethylammonio)methyl]azobenzene bromide (BisQ) is a potent agonist of the acetylcholine receptor (AcChoR) ofElectrophorus electrics. BisQ is highly constrained, suggesting that its structure is complementary to the combining site of the AcChoR when the latter is in its activated state. Antibodies produced in rabbits to a conjugate of bovine serum albumin and a derivative ofBisQ mimicked the binding characteristics of the AcChoR with respect to the order of binding of a variety of agonists and to the preferred recognition of decamethonium ion (an agonist) over hexamethonium ion (an antagonist). Immunization of three rabbits with purified anti-BisQ yielded antisera having binding characteristics of anti-AcChoR in that, by complement fixation and enzyme immunoassay, crossreactions with receptor preparations from rat, Torpedo, and eel could be demonstrated in sera ofall three rabbits immunized. Two ofthe three rabbits showed signs ofmuscle weakness similar to that seen after immunization with the AcChoR. One of the rabbits was injected intramuscularly with neostigmine and showed temporary improvement. Another showed post-tetanic exhaustion of hindlimb muscles after stimulation of the sciatic nerve at 50 Hz. Antibodies reactive with the AcChoR, therefore, were elicited by immunization with an antibody to a potent ligand of the AcChoR without the necessity of isolating the receptor itself. A similar mechanism may play a part in the etiology of at least some autoimmune diseases in which antibodies to various other receptors are involved.

Crime and Punishment in the Society of Lymphocytes: A Speculation on the Structure of the Putative Idiotypic Network

“…It should be noted that, in some cases, anti-ligand antibodies and physiological receptors have been shown to exhibit similar specificity pat terns (18). In the case of a self ligand-receptor system, it seems clear that an internal image of the ligand is an anti-S antibody because of its reactivity with the receptor combining site.…”

Idiotypy and autoimmunity

“…A majority of anti-DNA antibodies produced by lupusprone MRL-lprflpr and (New Zealand black x New Zealand white)F1 ([NZB x NZW]FI) mice express a CRI (16)(17)(18)(19)(20), as do the anti-DNA antibodies present in many humans with systemic lupus erythematosus (SLE) (21,22). CRIs have been identified on a high proportion of autoantibodies in the cerebrospinal fluid of patients with multiple sclerosis (23) and in the sera of patients with myasthenia gravis (24)(25)(26)(27). The majority of IgM anti-IgG antibodies which compose rheumatoid factors of patients with rheumatoid arthritis express the Wa Id (2).…”

Putative receptor for the plant growth hormone auxin identified and characterized by anti-idiotypic antibodies.

“…The animals were boosted at 2-week intervals with 0.5 mg of conjugate in incomplete Freund's adjuvant. The animals were bled from the ear vein after three boosts and the antibody titer was measured by a radioimmunoassay (19,20 For the production of anti-idiotypic antibodies (17,18), affinity purified anti-IAA antibodies (0.3 mg) emulsified in FCA were injected into NZW rabbits as described above.…”