Can immunoglobulin C(H)1 constant region domain modulate antigen binding affinity of antibodies?
Although the switch process is frequently associated with affinity maturation, the constant region is not assumed to play a role in Ag-Ab binding. In the present work, we demonstrate that two clonally related human monoclonal Igs sharing identical V(H) and V(L) sequences, but expressing different isotypes (IgA1kappa(PER) and IgG1kappa(PER)), bind tubulin with significantly different affinities. This difference was mainly accounted for by a disparity in the association rate constants. These results suggest that affinity maturation of this clone could be achieved through class switching in the absence of further somatic mutations. Since the differences observed were found at the Fab level, they also suggest a role for the C(H)1 domain in structuring the Ag-binding site into a more kinetically competent form.
Pritsch
O
O
Unité d'Immunohématologie et d'Immunopathologie, Institut Pasteur, Paris, France.
Hudry-Clergeon
G
G
Buckle
M
M
Petillot
Y
Y
Bouvet
J P
JP
Gagnon
J
J
Dighiero
G
G
D000595:Amino Acid Sequence; D000911:Antibodies, Monoclonal / Q000235:genetics; D000915:Antibody Affinity / Q000235:genetics* / Q000276:immunology; D000937:Antigen-Antibody Reactions / Q000235:genetics* / Q000276:immunology; D001483:Base Sequence; D001666:Binding Sites, Antibody / Q000235:genetics; D017252:CD3 Complex / Q000235:genetics; D006801:Humans; D017578:Immunoglobulin Class Switching / Q000235:genetics; D007127:Immunoglobulin Constant Regions / Q000235:genetics* / Q000276:immunology*; D007143:Immunoglobulin Heavy Chains / Q000235:genetics; D007132:Immunoglobulin Isotypes / Q000235:genetics; D007147:Immunoglobulin Light Chains / Q000235:genetics; D007135:Immunoglobulin Variable Region / Q000235:genetics; D007700:Kinetics; D013058:Mass Spectrometry; D008969:Molecular Sequence Data; D017421:Sequence Analysis; D014404:Tubulin / Q000276:immunology*
D000911:Antibodies, Monoclonal; D017252:CD3 Complex; D007127:Immunoglobulin Constant Regions; D007143:Immunoglobulin Heavy Chains; D007132:Immunoglobulin Isotypes; D007147:Immunoglobulin Light Chains; D007135:Immunoglobulin Variable Region; D014404:Tubulin