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.
Division of Hematology, University of Washington, Seattle 98195.
C B
CB
Brown
C E
CE
Hart
D M
DM
Curtis
M C
MC
Bailey
K
K
Kaushansky
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology*; D000915:Antibody Affinity; D000918:Antibody Specificity; D001665:Binding Sites; D003114:Colony-Forming Units Assay; D003115:Colony-Stimulating Factors / Q000276:immunology* / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D000939:Epitopes; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D006133:Growth Substances / Q000276:immunology* / Q000378:metabolism; D006410:Hematopoiesis; D006801:Humans; D051379:Mice; D011233:Precipitin Tests; D011487:Protein Conformation; D011863:Radioimmunoassay; D011956:Receptors, Cell Surface / Q000378:metabolism; D016184:Receptors, Colony-Stimulating Factor; D011994:Recombinant Proteins / Q000276:immunology
D000911:Antibodies, Monoclonal; D003115:Colony-Stimulating Factors; D000939:Epitopes; D006133:Growth Substances; D011956:Receptors, Cell Surface; D016184:Receptors, Colony-Stimulating Factor; D011994:Recombinant Proteins; D016178:Granulocyte-Macrophage Colony-Stimulating Factor