Two neutralizing monoclonal antibodies against human granulocyte-macrophage colony-stimulating factor recognize the receptor binding domain of the molecule

Using a series of mutant and chimeric human-mouse granulocyte-macrophage-CSF molecules the binding epitopes of two neutralizing mAb antibodies to human GM-CSF have been mapped. Both intact antibody and Fab fragments neutralize the biologic activity of human GM-CSF. The epitope of one of the antibodies contains residues widely separated in the primary structure of the growth factor that suggests that these two regions are adjacent in the tertiary structure of the molecule. In addition, evidence is presented that both mAb neutralize the activity of this cytokine by blocking the receptor binding domain of human GM-CSF.