Antiidiotypic antibodies mimic molecular and functional properties of human IL-1β 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-1β. mAb MhC1 and BrhC3 have been shown to inhibit binding of IL-1β to type I IL-1R, and to neutralize IL-1β 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-1β IL-1R and that this binding is inhibited by both IL-1β 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- 1β, 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.