Antiidiotypic antibodies mimic molecular and functional properties of human IL-1 beta in vitro and in vivo.
We obtained affinity-purified polyclonal anti-id antibodies against mAb MhC1 and BrhC3, which recognize amino acids 133-147 at the N-terminus of mature human IL-1 beta. mAb MhC1 and BrhC3 have been shown to inhibit binding of IL-1 beta to type I IL-1R, and to neutralize IL-1 beta bioactivity in a number of in vitro assays. We show that affinity-purified antibodies against the MhC1 and BrhC3 idiotypes specifically bind to type I IL-1 beta IL-1R and that this binding is inhibited by both IL-1 beta and IL-1ra; anti-id antibodies were also able to trigger IL-1R-dependent events, such as IL-8 secretion by human skin fibroblasts and pyrogenic effect after injection in mice. These anti-id antibodies, therefore, behave as structural and functional "images" of IL-1 beta, both in vivo and in vitro. These data indicate the idiotypic strategy as a powerful tool to study the fine specificity of receptor-ligand interactions. Moreover, this is, to our knowledge, the first report showing that the "internal image" of a cytokine can be active in vivo.
Molecular Immunoregulation Unit, DIBIT San Raffaele Scientific Institute, Milano, Italy.
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Soprana
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Vigo
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Verani
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Blom
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Siccardi
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Vercelli
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Viale
D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000276:immunology* / Q000302:isolation & purification / Q000494:pharmacology; D000911:Antibodies, Monoclonal / Q000276:immunology; D001667:Binding, Competitive; D002460:Cell Line; D005334:Fever / Q000209:etiology; D006801:Humans; D066298:In Vitro Techniques; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1 / Q000276:immunology* / Q000494:pharmacology; D016209:Interleukin-8 / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009500:Neutralization Tests; D011817:Rabbits; D017472:Receptors, Interleukin-1 / Q000037:antagonists & inhibitors; D012795:Sialoglycoproteins / Q000276:immunology
D000888:Antibodies, Anti-Idiotypic; D000911:Antibodies, Monoclonal; C507763:IL1RN protein, human; C507764:Il1rn protein, mouse; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D016209:Interleukin-8; D017472:Receptors, Interleukin-1; D012795:Sialoglycoproteins