Monoclonal antibodies specific for the IL-18 receptor

Interleukin-18, a pleiotropic cytokine is a member of the IL-1 family and has multiple immunoregulatory functions. IL-18 action leads to IFNgamma production by NK or T cells, induces Th1 differentiation and suppresses IgE synthesis by B cells when acting on responding cells in association with IL-12. At present two subunits of the IL-18R have been characterized: IL-18 Ralpha and IL-18 Rbeta. Both receptors belong to the IL-1R family. IL-18 Ralpha has been described as the ligand-binding chain and IL-18 Rbeta as the signal-transduction chain. Three monoclonal antibodies (mAbs) submitted to the HLDA8 workshop, designated H44 (80438), B-B46 (80228), and B-E43 (80232) were evaluated. The mAb specificity was determined by ELISA using coated recombinant IL-18 Ralpha or IL-18 Rbeta. Cell staining was analyzed by flow cytometry. A positive staining with the mAb B-E43 or H44 demonstrated that IL-18 Ralpha is expressed on several myeloid cell lines. No positive cell staining was observed with the anti IL-18 Rbeta mAb B-B46. The mAb biological activity was studied using the cell line KG1. A downmodulation of IFNgamma production was observed with the mAbs B-B46 (80228) and B-E43 (80232).