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.
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MESH: Amino Acid Sequence; MESH: Antibodies, Monoclonal; MESH: Tubulin; MESH: Antibody Affinity; MESH: Antigen-Antibody Reactions; MESH: Antigens, CD3; MESH: Base Sequence; MESH: Binding Sites, Antibody; MESH: Humans; MESH: Immunoglobulin Class Switching; MESH: Immunoglobulin Constant Regions; MESH: Immunoglobulin Heavy Chains; MESH: Immunoglobulin Isotypes; MESH: Immunoglobulin Light Chains; MESH: Immunoglobulin Variable Region; MESH: Kinetics; MESH: Mass Spectrometry; MESH: Molecular Sequence Data; MESH: Sequence Analysis; [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology
Journal articles; Life Sciences [q-bio]; Institut Pasteur; CNRS - Centre national de la recherche scientifique; CEA - Commissariat à l'énergie atomique; Institut de Biologie Structurale; HAL Grenoble Alpes; Direction de Recherche Fondamentale; Institut de Recherche Interdisciplinaire de Grenoble; CEA Grenoble
ISSN: 0021-9738; Journal of Clinical Investigation; https://hal.archives-ouvertes.fr/hal-00277598; Journal of Clinical Investigation, American Society for Clinical Investigation, 1996, 98 (10), pp.2235-43. ⟨10.1172/JCI119033⟩