Junctional amino acids determine the maturation pathway of an antibody

被引:131
作者
Furukawa, K
Akasako-Furukawa, A
Shirai, H
Nakamura, H
Azuma, T
机构
[1] Sci Univ Tokyo, Res Inst Biol Sci, Noda, Chiba 2780022, Japan
[2] Biomol Engn Res Inst, Osaka 5650874, Japan
[3] Tanabe Seiyaku Co Ltd, Discovery Res Lab, Yodogawa Ku, Osaka 5328505, Japan
关键词
D O I
10.1016/S1074-7613(00)80108-9
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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.
引用
收藏
页码:329 / 338
页数:10
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