Junctional amino acids determine the maturation pathway of an antibody.
We found that two distinct antibody maturation pathways exist in the immune response of C57BL/6 mice to (4-hydroxy-3-nitrophenyl)acetyl and that the junctional amino acid introduced by a process far preceding somatic hypermutation determined the pathway of affinity maturation. Antibodies belonging to each pathway clearly separated into two separate branches of a phylogenic tree. We also constructed a three-dimensional fitness landscape for antibody evolution by introducing the association constants of the antibodies into the phylogenic tree as the third axis, allowing us to comprehend the significance of junctional diversity in the "evolvability" of antibodies. Thermodynamic analyses of the antigen-antibody interactions suggested that a high conformational versatility in the antigen-combining site allows for the enhanced evolvability of antibodies.
Furukawa
K
K
Research Institute for Biological Sciences, Science University of Tokyo, Chiba, Japan.
Akasako-Furukawa
A
A
Shirai
H
H
Nakamura
H
H
Azuma
T
T
D000595:Amino Acid Sequence; D000596:Amino Acids; D000818:Animals; D000917:Antibody Formation; D001402:B-Lymphocytes / Q000276:immunology; D001483:Base Sequence; D002151:Calorimetry; D006241:Haptens / Q000276:immunology*; D006825:Hybridomas; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D009596:Nitrophenols / Q000276:immunology*; D010648:Phenylacetates; D017386:Sequence Homology, Amino Acid
D000596:Amino Acids; D006241:Haptens; D009596:Nitrophenols; D010648:Phenylacetates; C026242:4-hydroxy-5-nitrophenyl acetic acid