title: A role of the third complementarity-determining region in the affinity maturation of an antibody.
abstract: We recently found that there are two distinct antibody maturation pathways for the immune response of C57BL/6 mice to (4-hydroxy-3-nitrophenyl) acetyl and that a junctional amino acid introduced at a point far in advance of somatic hypermutation determined which pathway of affinity maturation was used. We describe here the structural basis for this aspect of maturation using recently developed H3 rules, which allow for reliable identification of the conformation of the third complementarity-determining region of the heavy chain (CDR-H3) from the primary amino acid sequences only. By the application of these rules, the anti-(4-hydroxy-3-nitrophenyl) acetyl antibodies examined here were classified into two major groups on the basis of their CDR-H3 structure, and these groups were found to be consistent with the maturation pathways. In addition, circular dichroism measurements revealed that the versatile nature of the antigen binding of the antibodies was significantly influenced by the pathway employed. We postulated in this study that flexibility in the CDR-H3 structure in the antigen-combining site could facilitate efficient antibody maturation supported by a plurality of possible antigen binding modes.
authors.affiliation: Research Institute for Biological Sciences, Science University of Tokyo, 2669, Yamazaki, Noda, Chiba 278-0022, Japan. furukawa@rs.noda.sut.ac.jp
authors.forename: K
authors.initials: K
authors.lastname: Furukawa
authors.forename: H
authors.initials: H
authors.lastname: Shirai
authors.forename: T
authors.initials: T
authors.lastname: Azuma
authors.forename: H
authors.initials: H
authors.lastname: Nakamura
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000737:chemistry / Q000276:immunology*; D000915:Antibody Affinity / Q000502:physiology*; D002942:Circular Dichroism; D022801:Complementarity Determining Regions / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008958:Models, Molecular; D011487:Protein Conformation
chemical_list: D000911:Antibodies, Monoclonal; D022801:Complementarity Determining Regions