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 j unctional amino acid introduced by a process far preceding somatic hypermut ation determined the pathway of affinity maturation. Antibodies belonging t o each pathway clearly separated into two separate branches of a phylogenic tree. We also constructed a three-dimensional fitness landscape for antibo dy evolution by introducing the association constants of the antibodies int o the phylogenic tree as the third axis, allowing us to comprehend the sign ificance of junctional diversity in the "evolvability" of antibodies. Therm odynamic analyses of the antigen-antibody interactions suggested that a hig h conformational versatility in the antigen-combining site allows for the e nhanced evolvability of antibodies.