Structure/function analysis of human interleukin 5 and its receptor.
We have performed a detailed structure-function analysis of human interleukin 5 (hIL5) and its receptor. By testing a hIL5 mutant panel in a solid phase binding assay and a proliferation assay using hIL5 dependent cell-lines, areas on hIL5 involved in either the receptor alpha-subunit interaction or in receptor activation were identified. Epitope mapping data of a neutralizing and a non-neutralizing monoclonal antibody were in agreement with the mutant analysis. hIL5 binding areas on the IL5R alpha-subunit were identified by interspecies chimaera analysis. Finally, hIL5 mutants with reduced receptor activation potential have antagonistic properties.
Tavernier
J
J
Roche Research Gent, Belgium.
Cornelis
S
S
Devos
R
R
Guisez
Y
Y
Plaetinck
G
G
Van der Heyden
J
J
D000818:Animals; D006801:Humans; D015848:Interleukin-5 / Q000737:chemistry / Q000502:physiology*; D051379:Mice; D015394:Molecular Structure; D009154:Mutation; D010446:Peptide Fragments / Q000737:chemistry / Q000502:physiology; D018123:Receptors, Interleukin / Q000737:chemistry* / Q000235:genetics / Q000502:physiology; D053649:Receptors, Interleukin-5; D013329:Structure-Activity Relationship
D015848:Interleukin-5; D010446:Peptide Fragments; D018123:Receptors, Interleukin; D053649:Receptors, Interleukin-5