Can immunoglobulin C(H)1 constant region domain modulate antigen binding affinity of antibodies?
| Autor: | J. P. Bouvet, Malcolm Buckle, Otto Pritsch, Jean Gagnon, Gilbert Hudry-Clergeon, Guillaume Dighiero, Yves Pétillot |
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| Přispěvatelé: | Immuno-Hématologie et Immunopathologie, Institut Pasteur [Paris], Physicochimie des Macromolecules Biologiques, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Institut de biologie structurale (IBS - UMR 5075 ), Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), Immunocytochimie, Institut Pasteur [Paris] (IP), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA) |
| Rok vydání: | 1996 |
| Předmět: |
MESH: Immunoglobulin Light Chains
CD3 Complex MESH: Antigens CD3 Antibody Affinity Immunoglobulin Variable Region MESH: Immunoglobulin Variable Region MESH: Amino Acid Sequence MESH: Tubulin MESH: Base Sequence Mass Spectrometry MESH: Antibodies Monoclonal Antigen-Antibody Reactions 0302 clinical medicine MESH: Antibody Affinity Tubulin MESH: Antigen-Antibody Reactions 0303 health sciences MESH: Kinetics biology Antibodies Monoclonal General Medicine MESH: Binding Sites Antibody Immunoglobulin Isotypes MESH: Immunoglobulin Class Switching Immunoglobulin Constant Region Antibody Immunoglobulin Constant Regions Immunoglobulin Heavy Chains Clone (B-cell biology) Sequence Analysis Research Article MESH: Immunoglobulin Heavy Chains Molecular Sequence Data Immunoglobulin light chain Affinity maturation MESH: Sequence Analysis 03 medical and health sciences Humans [SDV.BBM]Life Sciences [q-bio]/Biochemistry Molecular Biology Amino Acid Sequence 030304 developmental biology MESH: Mass Spectrometry MESH: Humans MESH: Molecular Sequence Data Base Sequence Immunoglobulin Class Switching Molecular biology Kinetics Immunoglobulin class switching MESH: Immunoglobulin Isotypes MESH: Immunoglobulin Constant Regions biology.protein Immunoglobulin heavy chain Immunoglobulin Light Chains Binding Sites Antibody 030215 immunology |
| Zdroj: | Journal of Clinical Investigation Journal of Clinical Investigation, American Society for Clinical Investigation, 1996, 98 (10), pp.2235-43. ⟨10.1172/JCI119033⟩ Journal of Clinical Investigation, 1996, 98 (10), pp.2235-43. ⟨10.1172/JCI119033⟩ |
| ISSN: | 0021-9738 |
| DOI: | 10.1172/jci119033 |
| Popis: | Although the switch process is frequently associated with affin- ity 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 iden- tical V H and V L sequences, but expressing different isotypes (IgA1 k PER and IgG1 k PER ), bind tubulin with significantly dif- ferent affinities. This difference was mainly accounted for by a disparity in the association rate constants. These results sug- gest that affinity maturation of this clone could be achieved through class switching in the absence of further somatic mu- tations. Since the differences observed were found at the Fab level, they also suggest a role for the C H 1 domain in struc- turing the Ag-binding site into a more kinetically competent form. ( J. Clin. Invest. 1996. 98:2235-2243.) Key words: im- munoglobulinsisotypeswitchingC H 1 • affinity |
| Databáze: | OpenAIRE |
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