ANTIIDIOTYPIC ANTIBODIES MIMIC MOLECULAR AND FUNCTIONAL-PROPERTIES OFHUMAN IL-1-BETA IN-VITRO AND IN-VIVO

We obtained affinity-purified polyclonal anti-id antibodies against mA b MhC1 acid BrhC3, which recognize amino acids 133-147 at the N-termin us of mature human IL-1 beta. mAb MhC1 and BrhC3 have been shown to in hibit binding of IL-1 beta to type I IL-1R, and to neutralize IL-1 bet a bioactivity in a number of in vitro assays. We show that affinity-pu rified antibodies against the MhC1 and BrhC3 idiotypes specifically bi nd to type I IL-1 beta IL-1R and that this binding is inhibited by bot h IL-1 beta and IL-1ra; anti-id antibodies were also able to trigger I L-1R-dependent events, such as IL-8 secretion by human skin fibroblast s and pyrogenic effect after injection in mice. These anti-id antibodi es, therefore, behave as structural and functional ''images'' of IL-1 beta, both in vivo and in vitro. These data indicate the idiotypic str ategy as a powerful tool to study the fine specificity of receptor-lig and interactions. Moreover, this is, to our knowledge, the first repor t showing that the ''internal image'' of a cytokine can be active in v ivo.