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 Printable version |
Functional epitope mapping of human interleukin-1 by surface plasmon resonance |
European Cytokine Network. Volume 8, Number 2, 161-71, June 1997, Articles originaux
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 Free Article
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Author(s) : C. D’Ettore, G. De Chiara, R. Casadei, D. Boraschi and A. Tagliabue |
Summary : A panel of monoclonal antibodies to human IL-1 has been used to probe its conformational and functional characteristics. Real time antibody-protein interaction was assessed by surface plasmon resonance with a BIAcore ® apparatus, in order to determine the kinetic and thermodynamic parameters of the interaction and to map the recognition sites of the antibodies on the IL-1 surface. Topological analysis was thus compared to the inhibitory capacity of antibodies for IL-1 bioactivity and binding to the activating receptor IL-1R I . This functional mapping analysis allows the following hypothesis. At least two discrete areas of IL-1 , located within the sequences 133-147 and 177-186 (as defined by mAbs MhC1 and BRhD2, respectively), are apparently involved in IL-1R I -independent agonist activity, and thus possibly take part in the interaction with the receptor accessory protein IL-1RAcP. Another area in the 133-147 sequence (defined by mAb BRhC3) is involved in agonist binding to its receptor CDw121a (IL-1R I ), whereas a site recognized by mAb BRhG5 within the sequence 218-243 is selectively responsible for non-agonist binding to the activating receptor. The loop between the 4th and the 5th-strand, at the open end of the IL-1-barrel structure, may possibly take part in both non-agonist binding to IL-1R I and in the interaction with IL-1RAcP. |
Keywords : antibodies, cytokines, cytokine receptors, surface plasmon resonance |
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