Schematic cartoon representation of vIL-6 structure.

(A) vIL-6 ABCD 4- helix bundle connected by peptide loops is displayed in different colors. Site I, composed of the N-terminal region of the AB-loop and the C-terminal region of helix D, identifies the epitope recognized by the vIL-6 neutralizing antibodies described here, and corresponds to the presumed site where hIL-6 would interact with IL-6R. Site II on helix A and C, and site III on the initial part of the AB-loop and helix D represent binding surfaces to gp130. (B) vIL-6 is juxtaposed to gp130 in a tetrameric (2:2) signaling model based on the crystal structure of the complex.22 vIL-6 site II is occupied by the D2D3 sites of one gp130 chain (yellow), and site III is occupied by the D1 site of another gp130 chain (red). Site I of vIL-6, comprising the outward helical face, is not occupied by gp130 and is sterically accessible for engagement by other molecules.