- 著者
- Tharanga MR RAMANAYAKE MUDIYANSELAGE Daisuke FUJIWARA Masataka MICHIGAMI Shunichi WATANABE Zhengmao YE Atsuko UYEDA Ryoji KANEGI Shingo HATOYA Ikuo FUJII Kikuya SUGIURA
- 出版者
- JAPANESE SOCIETY OF VETERINARY SCIENCE
- 雑誌
- Journal of Veterinary Medical Science (ISSN:09167250)
- 巻号頁・発行日
- pp.21-0318, (Released:2022-06-24)
Blocking the interaction between CD28 and B7 by cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) is a potent immune checkpoint that prevents damage to host tissues from excessive immune responses. However, it also significantly diminishes immune responses against cancers and allows cancer cell growth. This study found that recombinant (r) human (h) CTLA-4 specifically binds to canine dendritic cells (DCs) and suppresses the responses of canine T cells to allogeneic DCs. ERY2-4, a peptide targeting rhCTLA-4 selected from a yeast-displayed library of helix-loop-helix (HLH) peptides and improved to have a binding affinity to rhCTLA-4 as strong as that of rhB7, inhibited the binding of rhCTLA-4 to canine DCs. Furthermore, the targeting peptide significantly enhanced the response of canine T cells to allogeneic DCs. These results suggest that the CTLA-4-targeting peptide enhances canine T cell activity by blocking the interaction between canine CTLA-4 on T cells and canine B7 on DCs. This study demonstrates the generation of a new type of immune checkpoint inhibitor, which may be applicable to cancer therapy in dogs.
- 著者
- Masayuki Oda Takeshi Tsumuraya Ikuo Fujii
- 出版者
- 一般社団法人 日本生物物理学会
- 雑誌
- Biophysics and Physicobiology (ISSN:21894779)
- 巻号頁・発行日
- vol.13, pp.135-138, 2016 (Released:2016-07-14)
- 参考文献数
- 14
- 被引用文献数
- 2
We analyzed the correlation between the conformational strain and the binding kinetics in antigen-antibody interactions. The catalytic antibodies 6D9, 9C10, and 7C8 catalyze the hydrolysis of a nonbioactive chloramphenicol monoester derivative to generate a bioactive chloramphenicol. The crystal structure of 6D9 complexed with a transition-state analog (TSA) suggests that 6D9 binds the substrate to change the conformation of the ester moiety to a thermodynamically unstable twisted conformation, enabling the substrate to reach the transition state during catalysis. The present binding kinetic analysis showed that the association rate for 6D9 binding to the substrate was much lower than that to TSA, whereas those for 9C10 and 7C8 binding were similar to those to TSA. Considering that 7C8 binds to the substrate with little conformational change in the substrate, the slow association rate observed in 6D9 could be attributed to the conformational strain in the substrate.